Clinical based case reportsBy

Dr Azam Arzoo M.B.B.S (Bangladesh)Clinical Dissertation of Nephrology Sheffield Kidney Institute University of Sheffield

Under Supervision of Professor A M El Nahas Professor of Nephrology, University of Sheffield Sheffield Kidney Institute, Northern General Hospital Sheffield United Kingdom

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CONTENTSList of abbreviations Acknowledgement Dedication Abstract 1 Ward: RUE 1 multiple myeloma associated with hoarseness of voice: case report 2 ARF due to alcoholism: a case report 3 4 5 Reflux nephropathy: a case report Anemia management in CKD: a case report ARF secondary to fluid overload: a case report

PAGES 4 5 6 7 08-15 16-20 21-25 26-30 31-35

2 Ward: Vickers- 3 1 CKD related risk factor for CVD: a case report 2 3 4 5 3 Ward: 1 Vickers 2 and Transplantation IgA nephropathy and management: case report Acute kidney injury due to insect bite: case report Diabetic nephropathy and hypertension: case report P-ANCA positive vasculitis: case report

. . 36-39 49-48 49-53 54-57 58-62

Assessment and management of comorbid diseases in CKD: case 63-68 report Wegeners granulomatosis: case report 69-74

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Pulmonary hypertension in patients with ESRD on HD: case 75-78 report Risk of mortality for ESRD patients on dialysis: case report ADPKD: case report 79-83 84-88

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Ureteric stent( advantages and disadvantages): case report ATN after Transplantaion report case Psychotic disorders, after transplant: case report Delayed graft function and acute tubular necrosis (ATN): case report Post-transplant IgA nephropathy: case report

89-95 96-100 101-105 106-110

10 11 References

111-115 116-118

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List of abbreviationsAKI: CKD: ESRD: ESRF: DN: HTN: CRF: ANCA: ANA: GFR: ADPKD: GN: RRT: HD: PD: DM: IgAN: BP: IHD: S.Cr: SKI: DBP: SBP: ACEi: ARB: NSAID: DGF: CAPD: ATN: AR: CT: CIT: US: ASA: KUB: CVS: PMH: Hb: MCD: NIDDM: RUE : WG : JVP : Acute Kidney Injury Chronic Kidney Disease End stage of Renal Disease End Stage of renal failure Diabetic Nephropathy Hypertension Chronic Renal Failure Anti Neutrophil cytoplasmic antibody Anti Nuclear Antibody Glomerular filtration Rate Autosomal Dominant Polycystic Kidney Disease Glomerulonephritis Renal replacement Theraphy Haemodialysis Peritoneal Dialysis Diabetes Mellitus Immunoglobulin A Nephropathy Blood Pressure Ischaemic Heart Disease Serum Creatinine Sheffield Kidney Institute Diastolic Blood Pressure Systolic Blood Pressure Angiotensin Converting Enzyme Inhibitor Angiotensin Receptor Blocker Non Steroidal Anti Inflamatory Drug Delayed Graft Function Continious Ambulatory Peritoneal Dialysis Acute Tubular Necrosis Acute Rejection Computer Tomography Scan Cold Ischemic Time Ultrasonogram American Society of Anesthesiology Kidney Urinary Bladder Cardiovascular System Past Medical History Haemoglobin Minimal Change Disease Non Insulin Dependent Diabetes Mellitus Renal Unit E floor Wegerners Granulomatosis Jugular Venous Pressure

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ACKNOWLEDGEMENT First and foremost, praise be to Almighty ALLAH, the creator of the world, the beneficent and the most merciful. Without his help and guidance, this work, and every other work, would not be possible

My sincerest appreciation to Prof AM EL NAHAS, for affording me the opportunity to pursue this thesis in the department of Nephrology, Sheffield Kidney Institute, University of Sheffield and for his guidance and supervision all through the preparation of this thesis.

I would like to thank Dr Lutfi, Dr Kossi, Dr Brown, Dr Brenann, Dr Kawar, Dr Othman, Dr Parvez, Dr Amino Bello and Dr Ghada Said M. Omar

Finally, my deepest gratitude is due to my parents, brothers and sister for their love, prayer and continues encouragement throughout the course.

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Dedicated toMy mother Late Tasliman Nisa who scarifies her whole life to make me a doctor and dreamt for me to get specialized degree from England And her wish was that Before being a good doctor I should be a good human being

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Abstract Chronic kidney disease (CKD) is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression Objective: To distinguish the risk factors leading to kidney diseases through investigating different patients with kidney diseases (acute and chronic), and to describe the management of these patients with explaining the natural course of the disease. Design of the study: 20 in-patients diagnosed either with acute or chronic kidney disease, were participated in this study. The patients were randomly selected from Vickers-2, Vickers-3 and RUE in Northern General Hospital, Sheffield Kidney Institute, Sheffield, England, UK. The patients were fully aware of the objectives of the study. A complete physical examination for each patient was completed on the first session. A weekly follow-up and case report recording for each patient was followed for the length of the study (4 weeks). Main outcome measures: Most likely that the patients diagnosed with CKD of any stage converted into ESRD and therefore the patient might need renal replacement therapy in form of peritoneal or haemo-dialysis (PD or HD) or renal replacement therapy. This is only meant that patient might improve his or her quality of life but he/she complication nevertheless. Conclusion: Risk factors such as hypertension, diabetes mellitus, or aging (age >55) were the most common leading factors to chronic kidney diseases, however the risk of end stage renal disease among those patients was very low.

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A case report: multiple myeloma associated with hoarseness of voice

Introduction: Multiple myeloma belongs to a group of diseases known as the plasma cell dyscrasias, inwhich an uncontrolled proliferation of plasma cells, which elaborates a specific immunoglobulin molecule. These single clones of cells proliferate diffusely in the bone marrow, with associated bone destruction, but can give rise to a localized mass in bone, soft tissues, or both. Multiple myeloma accounts for 1% of all malignancies, with an incidence of four cases per 100,000, and accounts for 10% of hematologic malignancies. There are two important variants of multiple myeloma: solitary bone plasmacytoma and extramedullary plasmacytoma. Solitary bone plasmacytoma (SBP) is a localized intraosseous lytic lesion without marrow plasmacytosis. Extramedullary plasmacytoma is a plasma-cell tumor manifesting outside the bone marrow without evidence of systemic disease. Extramedullary plasmacytoma and solitary bone plasmacytoma have a better prognosis, and the patients are at least 10 years younger than those with multiple myeloma. Most authors think that SBP, extramedullary plasmacytoma, and multiple myeloma are different manifestations of the same disease. Progression of SBP and extramedullary plasmacytoma to multiple myeloma is the most important feature affecting the prognosis. The disseminated form, multiple myeloma, is by far the most frequent and has the worst prognosis of the three types.

Case Summary:A 59-year-old man admitted to the hospital after a sever deteriorating hoarseness of voice since 15 days. Patient came in RUE unit with complains of haemoptysis, rigth side pleuric chest pain and hoarseness of voice associated with shortness of breath. In addition the patient started coughing up blood since last 2 weeks. The cough is more in the morning with slight blood coming out with sputum. The patient advised by his general practitioner (GP) to analyze sputum sample. Bone marrow biopsy showed plasma cells

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Case Report:Name of the patient: B B Sex: male Age: 59 DOB: 25/09/1947: Present complain : Aware of diagnosis Feeling better HOPI Patient came in RUE unit with complain of haemoptysis, side pleuric chest pain and hoarseness of voice. Patient started coughing up blood since last 2 weeks. The cough more in morning blood is coming slightly coming with sputum. Patient went to his GP and GP advised him for sputum sample. Also complained right side pluraic chest pain. He also has history of shortness of breath, also noticed hoarseness of voice since last 15 days. Weight loss last 3 months but his appetite is good. No joint pain, no epitaxis no rash, no blood in urine, urine volume normal. No recent flu like symptom, no orthopnea. Dietian advised him low phosphorus diet and no added salt diet also fluid restriction. Reqested medic consider prescribing phosphate binder. Note hypercalcemia. Patient is now in dialysis using tunnel line on right atrium. No evidence of pneumothorax. Advising femoral line because tunnel has a complication of low chance of recovery.

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PMH: MGUS IgA nephropathy lamda in serum and urine 2001 had bone marrow biopsy COPD disease with bullae Emphysema left decoritication CKD 2 Pleural effusion left mini thoracotomy and plural biopsy, no malignancy found Personal history: Life long smoker, stoped in july in 06 Used to smoked 10/15/day Moderate alcohol consumption 6-8 pints/week

Allergy history No allergy history Family history Not significant Drug history Renagel 800mg BD Frusemide 250mg OD Na HCO3 50 mg BD

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Salbutamol 2.5 mg OD Paracetamol 1gm sos Recent therapy CORTICOSTERIODS CHEMOTHERAPY STEM CELL TRANSPLANTATION THALIDOMIDE BORTEZOMIB LENALIDOMIDE RADIATION THERAPY

On examination: BP- 125 /70 mm of Hg Pulse- 90 R/R-18 br/min Euvolumic JVP No sign of vasculitis No peripheral Sacral odema

CVS Heart sound normal

Respiratory 11

Chest clear Left thoracotomy scar

Abdomen Soft non tender

Investigation: 17/07/07 HB 11.6 HCT 0.38 WCC 5.3 PLTS 176000 ALK.PO4 109 TOTAL PROTEINS 68 NA 139 K 4.9 UREA 37.6 CR 478 CA 2.62 PO4 2.06 Renal function feb 2007 Urea- 6.4 and Crt-108 Worsening renal failure with Biopsy report Plasma cells constitute about 80% of the present and lie in confluent masses, extensive 80% infiltration by myloma

Differential diagnosis:12

Multiple Myeloma Amyloidosis Other Malignancy

DISCUSSIONMultiple myeloma is a plasma cell neoplasia. It is an incurable but treatable disease characterized by replacement of the bone marrow with malignant plasma cells, bone marrow destruction and paraprotein formation. This paraprotein is also known as the Mcomponent. This molecule is a homogeneous, partial or complete immunoglobulin. Based on the type of the M-component, multiple myeloma can be subdivided into the following types: IgG, IgA, IgD, IgE and IgM. Common clinical findings in multiple myeloma are hypercalcemia, anemia, renal damage, impaired production of normal immunoglobulins, osteoporosis and lytic bone lesions. The patient presented in this case had all of these symptoms. Additionally, multiple myeloma patients are at an increased risk of bacterial infections. The most common myeloma types are IgG and IgA, followed by IgD, IgE and IgM. There is also light chain disease where only light chains are synthesized, either kappa or lambda. Another variant is a nonsecretory myeloma with no M-component secretion.

Bone InvolvementThe bone lesions are formed as the tumor grows in the bone marrow and invades the hard bone creating the characteristic multiple small lytic bone lesions. The patient presented in this case already had back pain and on skeletal survey was found to have multiple lytic lesions. The severity of these lesions ranges from osteopenia to fractures. This bone destruction usually presents as bone pain, frequently in the lumbar spine.

Renal DiseaseMultiple myeloma causes renal failure in nearly 25% of patients. Hypercalcemia is the most common cause of renal failure, as it leads to tubulointerstitial disease. There is

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expression of the calcium receptor in the thick ascending limb of the loop of Henle where hypercalcemia inhibits reabsorption of calcium, magnesium and sodium chloride. In addition, hypercalcemia causes hypercalciuria via an increased filtered calcium load and suppression of parathyroid hormone release with a consequent reduction in calcium reabsorption.

Myeloma Cells and Bone Marrow Disease Myeloma cells are of the same type in any given person and produce large quantities of the same immunoglobulin protein, called monoclonal M protein, or paraprotein. When blood or urine is processed in electrophoresis, these M proteinsshow up as a "spike" in the results. The myeloma cells proliferate in the bone marrow and do not leave space for the normal B lymphocytes to develop and produce adequate immunoglobulins. This makes the patient prone to infections. Other cell lines are produced in smaller quantity. Fewer white blood cells and red blood cells are produced, and therefore patients present with anemia and susceptibility to bacterial infections.

Hyperviscosity Syndrome When the protein concentration in blood becomes very high the blood becomes very viscous, leading to flow problems. This is called hyperviscosity syndrome and some signs and symptoms of it are shortness of breath, confusion, chest pain, spontaneous bleeding and blurred vision. IgA myeloma causes hyperviscosity because of the predisposition of the IgA molecule to form dimers. Increased protein in the blood is what produces the classical roleaux finding (stacking of red blood cells) in the peripheral blood smear. The patient in this case was found to have multiple myeloma of the IgA type and she was experiencing hyperviscosity syndrome with symptoms of bleeding, shortness of breath and confusion. Both staging systems are of importance because they give prognostic values and aid in deciding when to start treatment. Treatment is tailored to each individual depending on several things, including the stage, physical exam and symptoms. The typical treatment is high dose chemotherapy and bone marrow stem cell transplantation. Adjunctive therapy 14

for myeloma is radiation therapy. Bisphosphonates are used against skeletal events because they inhibit bone resorption via action on osteoclasts or osteoclast precursors. Erythropoietin induces erythropoiesis and can be used to treat anemia from myeloma or from the chemotherapy. Plasmaphoresis may be done to treat the symptoms of hyperviscosity syndrome. Hydration sometimes is enough to treat hypercalcemia. Corticosteroids can be used to reduce swelling in patients with spinal cord compression due to multiple myeloma. Patients with acute renal failure benefit from dialysis, plasmaphoresis, management of hypercalcemia and avoidance of nephrotoxic medications. The standard chemotherapy regimen (VAD) combines vincristine, doxorubicin and dexamethasone. Another regimen commonly employed is (VBMCP) vincristine, bischloroethylnitrosourea, melphalan, cyclophosphamide and prednisone. MP (melphanprednisone) has also been used. Treatments currently in research include the use of interferon alfa to prolong remission. Thalidomide has recently been found to be an active agent in the management of multiple myeloma. Bortezomib (Velcade) is a reversible proteosome inhibitor that has also been used with good results. After several trials, the patient had the best response to a regimen involving regular hemodialysis and thalidomide-dexamethasone treatment. 1. Radiation therapy, used by some authors to the chest in combination with systemic therapy resulted in regression in the amount of effusion but no remission of myeloma. 2. Makino et al used intracavitary interferon-a (given at 5 MIU dissolved in 100 ml normal saline alternate days), and the patients effusion resolved after six treatments. Unfortunately, the patient died of myeloma about two months later, therefore this cannot be considered as standard. 3. The mainstay of therapy as of now is systemic chemotherapy. Reference: [1]

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Acute Renal Failure (ARF) due to alcoholism accombined with nonsteroidal antiinflammatory drug (NSAID): a case reportBack ground:Case of reversible acute renal failure (ARF) following binge drinking together with the transient use of a nonsteroidal antiinflammatory drug (NSAID) is described. After binge drinking, the patient experienced hyperdipsia, and the volume of his urine decreased. Subsequently, he took an NSAID to relieve systemic joint pain associated with low grade fever, and then he had complete anuria. One day after taking the NSAID, the patient admitted to the hospital after diagnosed with severe renal dysfunction accompanied by severe liver damage (blood urea nitrogen and creatinine concentrations were 57 and 5.4 mg/dl, respectively). The impaired renal function progressed over the first three hospital days, as reflected by an elevated creatinine concentration to ll.6 mg/dl. Nine treatment sessions of hemodialysis were, therefore, required to recover the loss of renal function. The present case suggests that binge drinking may be a potential risk factor for ARF.

Case summary:A case of middle aged male who developed swelling and weakness of muscles in the lower limbs following a heavy binge of alcohol is being reported. He had myoglobinuria and developed acute renal failure for which he was dialyzed. Acute alcoholic myopathy is not a well recognized condition and should be considered in any intoxicated patient who presents with muscle tenderness and weakness.

Case report:Name of the patient: S R G Age: DOB: 05/07/68

Present complain:

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Recent depression He has on haemodialysis Feeling well and no pain

HOPI: Patient came in hospital with history of aneuric and diagnosed ARF due to Rhabdomyolysis with Crt 598, Urea- 31.6, K-4.5, CK-804040 Early patient admitted in psychiatry dept in Barnsley Hopspital then he transferred in renal unit due to deterioration of renal function. Patient came back from Thailand had history of food poisoning over there after he so depressed and taking fluoxetine. In Thiland for 3 month early this year and he had history of unprotective sexual contact with female sex worker. No sign of compartment syndrome.

PMH Depression Ex alcoholic 5-6 pints/day Food poisoning while in Thialand early this year Developed diahorrea last 10 days Personal history Smoking 10-20 cigarate per day Alcohol consume 5-6 pint/day Family history Not significant Drug history: Omeprazole 10mg od

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Gliclazide 160mg bd Lisinopril 2.5mg od Metformin 1gm bd Sodium bicarbonate Calcichew 1.25 gm tds

On examination BP-160/90 mm of Hg Pulse: 78/min R/R- 17 br/min Peripheral edema present CVS Heart sound normal JVP not raised Respiratory Chest clear Abdomen Soft non tender

Investigation 14/07/07 HB 10.7 NA 138 K 5.4 CA 2.12 PO4 1.08 ALBUMIN 38 AST 18 HCO3 20

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USS Normal size of kidney

Diagnosis ARF due to Rhabdomyolysis

Discussion:Acute renal failure has been reported to be induced by alcohol ingestion alone. The case in this report showed evidence of non-traumatic rhabdomyolysis due to binge drinking. Severe muscle damage and extremely high levels of serum CK and myoglobin were observed in the cases of rhabdomyolysis-related ARF. In the present patient, the slight elevation of serum CKand myoglobin suggests that muscle damage might be less than that in the above-mentioned cases. Gabow et al reported that ARF is seen in 33% of patients with nontraumatic rhabdomyolysis, and dialysis therapy is required in only 15% of the cases They showed that anion gap (2814 mEq//) and phosphorus (7.3+3.5 mg/dl) in patients with rhabdomyolysis-related ARFwere higher than those in patients with non-rhabdomyolysisrelated ARF ( 1 76 mEq//, and 4.5 1.5 mg/dl, respectively) In the current report, the anion gap and phosphorus were 18.7 mEq// and 3.4 mg/dl, respectively. These results suggest that the patient had rhabdomyolysis, yet the muscle damage was not severe enough to induce dependent ARF requiring dialysis therapy. This, therefore, suggests that the reported case is not typical rhabdomyolysis related ARF. Experimental and clinical studies have revealed that volume depletion, which leads to activation of the pressor mechanism, appears to be a crucial factor in precipitating rhabdomyolysis induced ARF. Dehydration is a frequent consequence of heavy alcohol ingestion, because it is frequently accompanied by water dieresis, poor food and fluid intake and vomiting, especially in cases of severe binge alcohol ingestion. Furthermore, the majority of cases with rhabdomyolysis-induced ARF have manifested apparent body weight loss. The present patient, however, did not have a poor fluid intake nor suffered

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from any vomiting or apparent body weight loss before taking the NSAID, but he had hyperdipsia, dark urine and a decreased urine volume after binge drinking, suggesting that he was already in a mild dehydrated state before taking the NSAID. The increases in his hematocrit and total protein levels were slight, and FENa was more than 1%, making it difficult to suggest that the ARF was due to binge drinking alone. In fact, the patient had an episode of complete anuria following NSAID ingestion. The present case strongly suggests a linkage between alcohol-induced rhabdomyolysis and accelerates the impairment of renal hemodynamics. In summary, in the present study, it had been reported that a patient with acute renal failure following binge drinking in which case an episode of complete anuria following NSAID suggests that NSAID ingestion can accelerate the progression of impaired renal function induced by mild rhabdomyolysis, mild dehydration, and severe liver damage resulting in acute renal failure requiring dialysis therapy. It is therefore very important that physicians and pharmacists be alerted to the potential risk of NSAID induced acute renal failure when NSAIDs are ingested following binge drinking, even if patients have no severe muscle damage. In the future, further case reports will surely support our recommendation that the use of NSAIDs should be avoided.

Reference: [2], [3], [4]

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Reflux nephropathy : a case reportIntroduction:Reflux nephropathy (RN) as a cause of hypertension and end stage renal disease is being increasingly recognised. It leads to advanced renal failure in 30% of children and in 1520% of adults. The incidence of hypertension in children with RN ranges from 5 to 30%. It is important to realise that early detection of RN and long-term management of reflux can prevent both hypertension and end stage renal disease. Therefore, there is a need for increased awareness of this entity amongst the practising physicians so that cases are picked up early and by proper therapy adverse sequel of hypertension, chronic renal failure and end stage renal disease are prevented.

Case summary:A 63-year-old female suffer from hypertension was brought to Northern General Hospital with complaints of pain in abdomen, anorexia and was feeling unwell last 2 months. She had past medical history of urinary tract infection at the age of 5 years. Now she is feeling lethargy with weight loss. The patient lost her appetite for 3 consecutive days. She also feeling back pain around the lower spine area. She told that unable to walk much at home because of leg weakness. She could not movement facial muscle properly and limb as well. The patient neither was walking or speaking properly due to lethargy. On examination, she had a high blood pressure of 200/120 mmHg

Case report:Sur name : G D R Age: 63, Gender: Female

Present complain: feeling unwell last 2 months Lethargic for 2 month Loss of appetite and does not eat properly last 3 days Back pain around the lower spine 21

Log weakness unable to walk much at home

History of present illness: she is feeling unwell with lethargy and also losing weight day by day. She informed me that she does not ate for 3 days. She also feeling back pain around the lower spine area. She told that unable to walk much at home because of leg weakness. She could not movement facial muscle properly and limb as well She cant speak properly and also have evidence of weight loss.

Past medical history: Reflux nephropathy, HTN

Medication: Calcium gluconate 10% i/v Sodium bicarbonate 200mg tds 15 units actrapid in 50ml 50% dextrose Gelofusin 500ml i/v Augmentin 1.25 gms i/v One alpha .25mcgm od Social history: Lives with husband Not smokes since 27 yrs age She is working as a shop assistant and also she keeps cat/dog

On examination: BP: 127/56, Heart rate: 100 beat per minute

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CVS: Heart sound normal Respiratory system: Clear both lung Abdomen: soft tender lower abdomen

CNS: 3, 4, 6 intake 5 intakes 7 intakes 8-12 intakes

Investigation: 11/07/07 HB 12.1 HCT .36 WCC 5.3 PLATELETS 166000 ALK. PHOSPHATASE 105 TOTAL PROTEINS 61 NA 128 K 8.7 HCO3 24 UREA 24.2 CREATININE 428 USG: Bilateral small kidney, cortical scarring, no hydronephrosis Urea: 18.2, Creat: 449, K: 5.1

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ECG: tall T wave, broad QRS D/D: Acute rnal flure ---- 1. HTN 2. Reflux nephropathy CKD--- dehydration, sepsis

Discussion:In the recent literature, a lot of controversy surrounds the exact aetiopathogenesis of hypertension in RN. In this connection, the role of intra-renal reflux (IRR) should be emphasised. It has been shown that VUR alone does not lead to renal scarring. Renal scarring occurs only when VUR is associated with IRR. Factors favouring IRR are (i) association of UTI, (ii) association of high pressure VIR, (iii) the anatomical factors like compound and simple papillae. The compound papillae are more susceptible to IRR than simple papillae, due to anatomy of their orifice. How, the renal scarring leads to hypertension are still not thoroughly understood. In this connection the role of plasma renin activity needs to be discussed. In some patients with RN and hypertension the expected age related decrease in PRA, was not observed indicating that high PRA levels are contributing to hypertension. Another important factor is a focal increase in renin secretion and this can be demonstrated by analysing the segmental renal vein PRA. This segmental hyper secretion of renin may not be reflected in the renal vein PRA and yet they may be playing vital role in causing hypertension\. The reflux appears to be primary in our case. Whether this primary reflux is due to congenial abnormalities of the ureter and ureter orifices such as low ratio of intramucosal ureteric length to orifice diameter (Normal ratio 5: 1) could not be determined in our case as the parents were reluctant for cystoscopy which is necessary to identify such a congenital abnormality. For the diagnosis of RN, various imaging techniques have evolved both to demonstrate reflux as well as scarring. IVP can show scarring, but it can be normal in few cases. Dimercaptosuccinic acid (DMSA) scan is more sensitive than IVP in demonstrating scars. Medical Management of hypertension and primary reflux nephropathy consists of following plan: (a) Keeping the urine sterile by continuous prophylactic chemotherapy so as to prevent fresh scarring. In this report the patient was

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put on prophylactic chemotherapy with nitrofurantoin successfully. The drugs most commonly used are sulphamethoxozole -trimenthoprim, nitrofurantoin and sulphisoxazole. The prophylactic dose is one half of therapeutic dose. How long to continue the prophylactic antibiotic therapy? However, there is another view that if the reflux persists, the age of the patient should be an important determinant in deciding about the discontinuation of long-term chemotherapy. In late childhood and adolescent the disappearance of reflux, especially more than Grade III reflux is very much unlikely and in such a situation, chemo prophylaxis may be discontinued and surgery should be considered as a choice. (b) Hypertension should be treated by drugs, which decrease the renin production as the increased production of renin is shown to be the important factor in pathogenesis of hypertension. Hence captopril is very useful in hypertension. However, other drugs like propronol, methyl dopa have also been found useful. (c) Episodes of intercurrent infection may occur despite prophylactic chemotherapy. This should be vigorously treated with antibiotics, the type of antibiotics being used depending upon the culture and antibiotic sensitivity. The role of surgery in the management of RN is beset with controversy. Surgical success rate for elimination of reflux is quiet high for all grades of VUR: 90-100% for Grades I and II, 93-99% for Grade III and 50-60% for Grade IV and V. The patients showing VUR with or without demonstrable scarring should be given prophylactic chemotherapy to keep urine sterile (The scar may take several months to be demonstrable either by IVP or DNISA scan.

Reference: [5]

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Anemia management in CKD: a case reportIntroductionAnemia is common in chronic kidney disease (CKD) due to a state of erythropoietin deficiency. Erythropoietin therapy has been used for approximately 20 years to correct anemia in CKD and to improve both subjective and objective outcomes. Guidelines that establish a hemoglobin (Hb) goal for anemia correction in CKD patients are largely based on observational data. Controversy still exists, however, because outcomes have not been consistent with various degrees of anemia correction. The number of prospective randomized trials investigating the effects of anemia correction on cardiovascular (CV) morbidity and mortality in CKD patients, an already high-risk group, is limited. With respect to improving CV outcomes in the CKD population, the currently available trial data caution against raising Hb levels in CKD patients to approach more "normal" physiologic ranges. The disappointing experience with the trial data must be weighed against the beneficial associations of erythropoietin therapy that have been generated from observational data. Establishing the ideal target Hb ranges for anemia correction in CKD patients remains a dynamic process and leaves many gray areas to be further elucidated. Chronic kidney disease (CKD) has been linked to higher heart failure (HF) risk. Anemia is a common consequence of CKD, and recent evidence suggests that anemia is a risk factor for HF. In this study a case reported to show the association between CKD and anemia.

Case summary:A 82-year-old man with hypertension was initially feeling tired and breathless from last few days. His blood report suggesting severe anaemia 4.6 g/d. renal ultrasound revealed severe bilateral hydronephrosis. In addition, he had history of prostectomy 5 years back and CKD-5. He also has Pedal oedema and clubbing. He was referred to our institution 26

for further evaluation and management of his persistent symptom of severe anaemia, dry cough and mild epitasis for last few months, shortness of breath, loss of appetite and weight loss.

Case report:Surname: L H First name: R Age: 82 yrs Male

Present complain: Feeling tired and breathless from last few days

HOPI: Normally he is well and no medical illness. Look after his wife for last 2 months who had a stroke, feel loss of appetite and weight loss. For last few days feeling tired and shortness of breath.. Today feel more unwell. His blood report suggesting severe anaemia 4.6 g/d. He also complained about dry cough and mild epitasis for last few months. He also denied previous renal failure, urinary symptom and peptic ulcer symptom.

PMH: HTN Prostate operation 5 years back CKD stage 5 Drug history: Venofer 100mg /month Neorecormon 4000i.u 2/week Atorvastatin 40mg od Alfacalcidol 1mcg od

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Sodium bicarbonate 50mg One alpha 0.25mcg od Ramipril 2.5 mg Allergy history: NAD O/E: Pale looking BP: 106/55, Pulse: 80, Heart rate-100/min, Sats 96% Pedal oedema present Thin comfortable, Clubbing-present Dehydration Lung: Clear CVS: Normal HS Abdomen: Soft, non tender P/R: no melena Catheter: Turbid urine

Investigation: HB 9.1 WCC 10.2 PLTS 182 MCV 87.1 NA 132

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K 4.6 UREA 10.2 CR 186 Ca 2.0 PO4 2.1 ALK PO4 58 ALBUMIN 38

ECG- No evidence of hyperkalaemia yet Urine dipstick: Blood 2+, Protein- 2+, Leu 2+ USS: Right Kidney measure 10.1 cm and is hydronephrotic renal pelvis measuring 1.5 cm Left kidney measure 8.9 cm and also grossly hydronephrotic and proximal ureter dialated as well. Left renal pelvis measure 3.5 cm. Bladder catheter in situ No mass lesion seen Comment: Bilateral severe hydronephrosis, cortical thinning probably long standing.

Discussion:Anaemic patients with chronic renal failure should receive treatment with recombinant human erythropoietin (r-HuEPO, Eoetin) to maintain hemoglobin levels over 11 g/dL with an acceptable target of 12 to 12.5 g/dL, according to recommendations from the European practice guideline for management of anemia in patients with chronic renal failure [33] and the National Kidney Foundation K/DOQI clinical practice guidelines for anemia of chronic kidney disease [27]. Benefits of adequate hemoglobin levels had been established in patients undergoing dialysis, and are supposed to be relevant also in CKD patients. In addition, anemic patients should receive iron supplementation in order to maintain serum ferritin levels above 100 g/L and transferrin saturation above 20%.

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The CHOIR and CREATE studies, together with previous randomized controlled trials in patients on dialysis, indicate that we should aim for only partial correction of anemia in patients with CKD, and that 115 g/l (11.5 g/dl) is a reasonable upper limit for a hemoglobin target. It is important to recognize that, because of the difficulty of maintaining hemoglobin concentrations within a narrow window, reducing the upper limits of hemoglobin targets is likely to increase the proportion of patients with hemoglobin concentrations less than 110 g/l (11.0 g/dl), and perhaps even the proportion with levels below 100 g/l (10.0 g/dl). The ongoing Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), which allows a hemoglobin level as low as 90 g/l (9.0 g/dl) in one treatment arm, should provide important information about acceptable lower limits.

ConclusionIn conclusion, further evidence was found that the concomitant presence of either CKD or anemia increased the risk of dying in the hospital or of being readmitted within 30 days among patients hospitalized with heart failure. The association persisted after controlling for other factors associated with adverse outcomes in these patients.Patients with anemia caused by CKD are at higher risk of death or cardiovascular events when the target hemoglobin level is 135 g/l rather than 113 g/l. Reference: [6], [7]

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ARF secondary to Fluid overload: a case reportBackground:Fluid overload is a chronic, troublesome problem in many patients on hemodialysis. These patients suffer from hyperdipsia with inability to excrete water. Angiotensinconverting enzyme inhibitor (ACEI) has been shown to decrease thirst and interdialytic weight gain in 2-4 weeks of usage. It was suggested that long-term ACEI may not continue to suppress inappropriate thirst and fluid intake after 6 months in hemodialysis patients.

Case summary:A 19-year-old male patient with untreated seizure disorder, presenting with Nausea, vomiting, loss of appetite and weight loss for 2 weeks, and impaired renal function Urea- 213, Creat 743, K-4.2 Usually fit and well started with nausea, vomiting for 2-3 weeks and also has history of haemetemesis. He also complain about haematuria and dysuria, He mentioned that he suffer from decreased urine output. He also was complaining of joint pain but not redness or swelling of joint. He had productive cough with slight haemoptysis 2 weeks ago. No recurrent nose bleeding reported. Patient was referred with lethargy with increased urea and Creatinine. USS abdomen showed right kidney 10.1 cm and left kidney 9.3 cm. No hydronephrosis. Renal biopsies was arranged but cancelled twice because of increase bleeding time in spite of having DDAVP. Urea and Creatinine remain stable throughout his stay in the hospital. Follow up is arranged in the low clearance clinic in 3 weeks time.

Case report:Name: B S M Age: DOB:30/08/1988 31

Present complain: Nausea, vomiting, loss of appetite and weight loss for 2 weeks Impaired renal function Urea- 213, Creat 743, K-4.2 HOPC: Usually fit and well started with nausea, vomiting for 2-3 weeks and also has history of haemetemesis. He also complain about haematuria and dysuria, He told me that he also has decreased urine output. He has also complaining joint pain but not redness and sweeling of joint. He also informed me has cough with sputum but had slightly haemoptysis 2 weeks ago. Otherwise no recurrent nose bleeding. Patient is being refer with feeling unwell and had increased urea and Creatinine. USS abdomen showed right kidney 10.1 cm and left kidney 9.3 cm. No hydronephrosis. Renal biopsy arrange but cancelled twice because of increase bleeding time inspite of having DDAVP. Urea and Creatinine remain stable through out his stay in the hospital. Follow up is arranged in the low clearance clinic in 3 weeks time.

PMH: He had episode of constant vomiting for 2 months 2 years ago No further investigation and treatment at that time has taken.

Drug history: Frusemide 160mg bd Prednisolone 15mg od One alpha 250mcg Pravastatin 20mg od Septrin 200mg od Inj. Eprex 2000 i.u 3/week Spironolactone 500mg od Oral antacid syrup from GP either nil else Allergy history:

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Nil Family history: Lives with parents Smokes 10/day Occasionally drinks alcohol. No family history of renal disease and DM 2 cousins have hearing loss and wear hearing aids O/E: BP: 153/86, Sats-98%, Weight 71.4, Pulse-104/min CVS: Systolic murmur present Lung: Clear Abdomen: Soft non tender

Investigation: 16/07/07 HB 9.3 WCC 13.1 PLTS 454000 MCV 96.3 ESR 108 PT 16 APTT 40.2 PTH 123 UREA 20.3 CR 319 CA 2.61 PO4 1.8 K 4.7 NA 136 USS: 33

Both kidney measure appro 10.1 cm Right 9.3 cm Left No abnormality of kidney and no hydronephrosis Bleeding time: more than 10 minutes Urine Dipstick Blood Protein more than 300 mg/dl Glucose negative D/D ARF RPGN

Discussion:Volume overload should be suspected in patients complaining of dyspnea, chest discomfort, orthopnea, paroxysmal nocturnal dyspnea, or progressive decrease in exercise tolerance. It may also be asymptomatic. Physical findings could include jugular venous distention, hepatojugular reflux, pulmonary rales, wheezing (in cardiac asthma), and S3 or S4, ascites, and peripheral edema. Patients with chronic kidney failure may also have significant volume overload even in the absence of the above symptoms and signs. Chest films may show evidence of pulmonary edema or may be subtle, showing only prominent pulmonary vasculature. The same findings may occur with heart failure, liver failure and various other conditions, so the patients change in weight over time is critical. Over weeks to months, these patients may lose lean body mass due to malnutrition and can develop fluid overload with relatively little change in weight. Therefore, serial assessment of patients lean body mass is also critical.

Contributors include:

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Excess salt intake Progressive kidney damage (nephrosclerosis) Fluid retention from blood pressure medications Inadequate diuretic therapy.

Consider fluid overload for sudden unexplained gains in weight, refractory hypertension, peripheral edema or shortness of breath. These may be secondary to the above causes. Hyponatremia, developing as a result of water retention in excess of sodium retention, may also be a marker for volume overload in the above setting. Management: Patients should be weighed at every visit Dietary sodium restriction to 2 gm/d Loop diuretics, and if refractory to twice a day dosing, consider adding thiazide-type diuretics If advanced kidney failure, consider initiation of dialysis.

Reference: [2]

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Chronic kideny disease (CKD) related risk factor for cardiovascular disease (CVD): a case report

Back ground:Patients with CKD have many of the traditional risk factors for CVD, including older age, hypertension, dyslipidemias, diabetes mellitus, and physical inactivity (Menon, Gui, & Sarnak, 2005). Age is the only one of these traditional risk factors, shared by many patients with CKD, that is not modifiable. Other nonmodifiable CVD risk factors include gender, family history, and hereditary factors such as race. Hypertension, dyslipidemias, diabetes mellitus, smoking, and physical inactivity, risk factors, that adversely affect other risk factors, such as obesity and hypertension, can all be managed or treated, thus are considered modifiable risk factors (Grundy et al., 1999). In addition to traditional CVD risk factors, individuals with CKD must also be assessed for nontraditional risk factors. Many of the complications of CKD, when not adequately treated, may lead not only to more rapid progression of kidney disease but, also, to increased cardiovascular morbidity and mortality (NKF, 2005). These unique CKDrelated risk factors for the development of CVD include anemia, proteinuria/microalbuminuria, disturbances of mineral metabolism, extra cellular volume overload, malnutrition, inflammation, elevated homocysteine levels, and elevated creactive protein levels (Abramson, Jurkoutz, Vaccarino, Leveintraub & McClellan, 2003; Cullerton et al., 1999; Sarnak et al., 2003; Shlipak, Fried, Stehman-Breen, Siscovick, & Newman, 2004). The Kidney Disease Outcome Quality Initiative (K/DOQI) Guidelines recommend consideration of all of these unique risk factors and suggest that efforts to reduce CVD risk should be initiated early in the course of CKD to reduce morbidity and mortality (NKF, 2005).

Case summary:A 75-year-old man of British origin, was admitted to renal unit at Northern General Hospital for further evaluation of chronic kidney disease (CKD). He has no history of

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diabetes mellitus or hypertension but nocturia 4 times per night. He had history of CKD with progressive incline of creatinine from 136 mmol/l in 2005 to 200 mmol/l in December 2000. Lately a creatine of 153 mmol/l and GFR 38ml/min (CKD) was reported.

Case report:Name: D P Age: 75 Occupation: retired Gender: male HOPI: The patient suffer from shortness of breath, wheeze, hotness, sweaty and dizziness upon standing. Also he felt chest tightness across the chest. There is no history of DM, haematuria but nocturia 4 times per night. Pheripheral oedema is intermittently a problem through is currently well control with just 2 mg of bumetanide. There is no definitive history of orthopnea or paroxymal nocturnal dyspnea. Though he is markedly dyspnea on walking a few yards. H/O CKD with creatinine climbing from 136 mmol/l in 2005 to 200 mmol/l in December. From this clinic visit he had a creatine of 153 mmol/l and GFR 38ml/min (CKD) Past history: CKD, AF, CF No history of DM, stroke, weakness, numbness, coughs, diarrohea, vomiting and leg swollen. Medication: there is recent NSAID used, no allergy drugs. Bisoprolol fumarate 3.75 mg tab Bumetanide 1 mg tab Ramipril 5 mg

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Bumetanide 1mg Warfarin WBS 1mg Simvastatin 20 mg Omacor 1g Personal history: Ex smoker who drink 5 pints 2 times weekly through was previously a heavier drinker. He lives a lone but has a stair O/E: Pulse BP CVS: S1 and S2 heart sound normal. JVP not visible. Respiratory: Trachea centrally. Few basal crepitation present. GIT: abdomen is soft , no tender and rigidity. Investigation: Na- 139, K- 4, Urea- 10.1, Creat- 147, HCO3- 33, Ca- 2.32, PO4- 1, CaPO4- 2.32, AlkPO4- 87, AST- 40, Bilirubin- 17 Hb- 15.4, WCC- 10.2, MCV-94.3, MCH- 31.1, MCHC- 32.9

Discussion:There are guidelines available to direct the practitioner in reducing a patient's cardiovascular risk factors. The National High Blood Pressure Education Program of the NIH presented its Seventh Report of the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in 2004 (USDHHS, 2004). Like its predecessors, these JNC 7 Guidelines provide an evidence-based approach to the prevention and management of hypertension, a major risk factor in the development of CVD as well as CKD (Chobanian et al., 2003). The American Heart Association (AHA) Guidelines for Primary Prevention of

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Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients without Coronary or Other Atherosclerotic Vascular Diseases provides a framework to assist primary care providers in assessment, management, and follow-up of patients who may be at risk for but who have not yet manifested cardiovascular disease (Pearson et al., 2003). Although the JNC 7 Guidelines and the AHA guidelines provide a framework for comprehensive care for the general population of patients at risk for CVD, they do not specifically address all of the CKD-related nontraditional CVD risk factors. The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) Executive Summary was released in 2001 (ATP III, 2001). Based on the ATP I and APT II, these were updated, evidenced-based clinical guidelines. They provided direction for cholesterol testing and management that expanded the indications for intensive cholesterol-lowering therapy in clinical practice and applied findings from the most recent clinical trials. While ATP III maintained attention to intensive treatment of patients with CHD, its major new feature was a focus on primary prevention in persons with multiple risk factors. Because of the focus on individuals with multiple CHD risk factors, the guidelines can be applied to the population of patients with CKD. However, they do not specifically address this group or CKD-related risk factors. In 2005, in an effort to more effectively address the risk of CVD in patients with CKD, the National Kidney Foundation (NKF) developed the K/DOQI Guidelines for Cardiovascular Disease in Dialysis Patients (NKF, 2005). The K/DOQI Guidelines recommend that CVD risk factor reduction should be initiated early to reduce morbidity and mortality associated with CKD. The guidelines for treatment and prevention are specific to individuals with Stage 5 CKD, and the extent to which they can be applied to persons in the earlier stages is unclear.

Reference: [8], [9], [10]

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IgA nephropathy management: case reportBack ground:IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to (ESRD). Despite the need for effective treatment strategies, very few Randomized Control Trial for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, that contain a high concentration of omega 3 fatty acids. While ACEi are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity

Case summary:A 36-year-old man was referred to the Department of Nephrology at the Northern General Hospital (Vickers 3) because of an episode of asymptomatic gross proteinuria suggesting nephritic syndrome with a serum albumin of 21, serum protein of 51.2; clinically she had edema in mild shin on review clinic. The patients Alanine Transferase which returned back to normal. In addition her Anti Nuclear Antibody and Ig A antibody were positive. The patient had no family history of renal disease. Biopsy results showed.

Case report:Name: B P Age 60 yrs Chief complain: post biopsy, passing urine HOPI: The patient was feeling unwell recently. She also complained of back pain of dullache nature over the last year and, taking pain killer. She attached anxiety last year and last

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night she had physiotherapy. After holiday in Turkey in October 2006 she began to complain arthralgia, ankle swelling and severe lethargy. She did have transient upper GI symptom which settle with OPI. She had went a normal OGD and colonoscopy in 2006. Her urine dipstick was positive for protein in a 24 hrs. urine collection at 3.22 for in 24 hrs of protein. Suggesting nephritic syndrome with a serum albumin of 21, serum protein of 51.2, clinically she had odema in mild shin on review clinic. Her ALT which her now settle back to normal. In condition, her ANA was positive, Crt-54, Na- 136, Urea-4.8. She also positive Ig A antibody, low Ca 2.17 She denies any diarrohea, haematuria, previous recurrent UTI, renal stone, flank abdominal pain, she denies facial rashes, red dry eyes, sore throat. She has not had a blood transfusion in past. She denies an any past history of IHD, DM,CVA, malignancy, asthma, COPD Family history: there is no history of kidney disease. She only smoke for a year or when she is very young but has not smoke last 50 yrs. She takes very minimum amount of alcohol. She did biopsy and waiting for biopsy report. HPH: hypothyroidism, proteinuria, microscopic haematuria, HTN Treatment Alfacalcidol 1 mcg od Gliclazide 40mg od Neorecormon 4000i.u / week Clonazepam 50 mcg od Lactulose + senna O/E: Pulse 72 beats/min BP 130/70 mm of Hg CVS: S1 and S2 heart sound normal. JVP not visible. Respiratory: Trachea centrally. Chest clear

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GIT: abdomen is soft, no tender and rigidity

Investigation: HB 10.8, WCC 12.1, PLTS 196, MCV 91.6, NA 136 K 4.6, UREA 10.2, CR 199, HCO3 21, CA 2.1 PO4 1.45, ALK.PO4 58, ALBUMIN 38

Discussion:Patients with IgAN usually present with hematuria. Approximately 40% to 50% of patients have macroscopic hematuria frequently accompanied by an infection of the upper respiratory tract and, less often, pneumonia, gastroenteritis, or urinary tract infection. The episode is usually briefabout 24 hoursbut can last as long as 1 week. This feature usually occurs in children and in patients under 40 years of age, and loin pain often accompanies the hematuria. Microscopic hematuria, usually with proteinuria, constitutes the other common initial presentation in another 30% to 40% of patients. Macroscopic hematuria can complicate the course of about 20% to 25% of patients in this subgroup. This presentation is more common in older patients but is observed in patients of all ages. As many as 20% of patients with IgAN present with severe azotemia that represents long-standing disease. Acute renal failure occurs in less than 10% of patients, and the nephrotic syndrome is uncommon, occurring only in approximately 5% of all patients, usually children and adolescents. The diagnosis of IgAN currently can be made only by kidney biopsy. The spectrum of light microscopic findings ranges from minor mesangial changes to focal and diffuse mesangial proliferation to crescentic glomerulonephritis. In addition to glomerular lesions, various tubulointerstitial and vascular lesions also can be seen, including tubular atrophy, interstitial fibrosis, interstitial cellular inflammation, and vascular sclerosis. However, the histopathologic criterion for IgAN is the dominance or co-dominance of IgA deposition in the mesangium. Although many other diseases also are associated with glomerular IgA deposits5, I will not consider their prognosis and treatment in this review.

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Table 1. Clinical risk factors for progression in IgA nephropathy (IgAN) Impaired renal function at discoverya Magnitude and duration of proteinuriaa Hypertension at presentationb Older age at onset Absence of recurrent macrohematuria Persistent microscopic hematuria Male gender Obesity Hyperuricemia Hypertriglyceridemia Smoking Familial disease

Table 2. Histologic risk factors for progression in IgA nephropathy (IgAN) Glomerular Advanced glomerulosclerosisa Mesangial hypercellularity Segmental necrotizing lesions Extensive crescents (>30%) Capillary wall deposits of IgA Tubulointerstitial Marked tubulointerstitial fibrosisa Intense interstitial infiltration Arteriosclerosis/arteriolosclerosis

The magnitude and character of proteinuria are powerful clinical indicators of an adverse outcome. At present, it is believed that no sharp dividing point relates the magnitude of proteinuria to prognosis. Most investigators, however, believe that more than 1 g/day is a

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reasonable threshold for concern11,15. Universal consensus exists that proteinuria >3 g/day is associated with a high likelihood of a subsequent progressive decline in renal function Less concordant are the data for the prognostic value of arterial hypertension at presentation. High blood pressure (>140/90 mm Hg) can be an important factor associated with a more rapid progression in adults with IgAN. However, when this clinical factor was evaluated using multivariate analysis in several studies, it appeared to be significant in some but not all

TreatmentThe patients with IgAN with normal renal function, minimal (1 g/day, slowly progressive renal failure, and moderate to severe changes in renal biopsy histology could be candidates for one or even several therapeutic modalities. There are many approaches to treat adults with primary IgAN includes the following:

ACE inhibitorsControl of blood pressure remains the cornerstone of treatment as for patients with other types of kidney disease. The therapeutic benefit of antihypertensive drugs is thought to be a putative reduction of glomerular hypertension that provides protection against glomerular injury. Because of their ability to specifically reduce intraglomerular pressure, ACE inhibitors have attracted the most attention as the ideal antihypertensive drugs for the treatment of hypertension in renal disease, including IgAN. The effectiveness of ACE inhibitors in reducing progression of renal dysfunction is posited to be a consequence of their antiproteinuric effect rather than attributable to their blood- pressure-lowering effect alone. Moreover, ACE inhibitors also might attenuate the effect of angiotensin II on renal cell growth and proliferation and might inhibit extracellular matrix component release that culminates in sclerosis.

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SteroidsSteroids were among the first agents used for the treatment of IgAN. In an early, randomized, prospective, controlled trial in adult patients with IgAN and the nephrotic syndrome, 4 months of therapy with moderate doses of oral steroids did not produce any benefit except in patients with very mild histologic lesionsAlso, Kobayashi et al reported beneficial effects of steroids given in moderate doses for periods of 1 to 3 years in patients with moderate or heavy proteinuria. In both studies, renal function was preserved in patients with an initial creatinine clearance of >70 mL/min but not in those with more severe impairment of renal function. The same authors also have demonstrated that daily steroids for 18 months in IgAN patients with normal renal function and moderate proteinuria produced a better preservation of renal function and a greater reduction in proteinuria 10 years after therapy when compared with an untreated group.

Immunosuppressive drugsThere is limited experience with the use of azathioprine in the treatment of IgAN in adults. Goumenos et al published a retrospective study that used long-term azathioprine combined with low-dose prednisone in patients with progressive renal disease accompanied by proteinuria and moderate to severe histologic changes. Eighty percent of patients receiving azathioprine exhibited stable renal function, but only 36% of the group treated conservatively. There was no effect on proteinuria.. Cyclophosphamide has been used in a limited number of trials. Some of these studies used a combination of cyclophosphamide, dipyridamole, and warfarin and chiefly showed a reduction in proteinuria. Cyclosporine was tested in a randomized single-blind trial conducted by Lai, Lai, and Vallance-Owen. The drug was given for 12 weeks to 24 patients with proteinuria of at least 1.5 g/day and reduced renal function. They showed a modest reduction in proteinuria, unfortunately often accompanied by a rise in serum creatinine. These changes were reversed after cessation of the treatment. Thus, while cyclosporine is likely to display an antiproteinuric effect in IgAN, the risk of nephrotoxicity limits its usefulness. 45

Limited trials of mycophenolate mofetil (MMF) have been reported. In a few case reports and a small uncontrolled trial, MMF, 1 to 2 g/day alone or combined with steroids for several months, decreased proteinuria and stabilized serum creatinine in patients with severe IgAN

Fish oilInterest in fish oil as a treatment of IgAN has recently intensified. Fish oil is rich in -3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These compete with arachidonic acid and produce biologically less-effective prostaglandins and leukotrienes that might retard renal damage by decreasing glomerular and interstitial inflammation, platelet aggregation, and vasoconstriction. In the United States, a randomized controlled trial is underway comparing fish oil, alternate-day prednisolone, and ACE inhibitors in children and young adults with IgAN. The results of this trial should considerably clarify whether steroids or fish oil is better for patients at risk for progressive renal disease.

Anticoagulant and antiplatelet drugsAnticoagulant and antiplatelet therapy have long been used in the treatment of IgAN. Most of the early trials were uncontrolled and small in size.

Other treatment considerations Tonsillectomy also has been recommended for patients with IgAN, but its role remainscontroversial. Removal of the tonsils in patients with chronic or recurrent tonsillitis reduces serum IgA levels, circulating immune complexes, proteinuria, and episodic hematuria. Patients most likely to benefit from tonsillectomy had preserved renal function (serum creatinine 12 g/dl did not improve measures of quality of life and may increase the risk of cardiovascular events. Additional clinical studies are ongoing to try to provide guidance in this complex area.Abnormal calcium and phosphorus metabolism may also be present in patients with CKD. These measures, along with measurement of intact-parathyroid hormone (i-PTH),

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may identify bone disease related to CKD. Bone disease may lead to poor bone structure resulting from high or low turnover, and this may result in a higher risk of fracture. Frequency of measurement of calcium, phosphorus, and i-PTH is described in The target serum phosphorus goal is < 5.5 mg/dl in patients with Stage 5 CKD and < 4.6 mg/dl in Stage 3-4 CKD. In Conclusion: CKD and diabetes are common diseases that affect a large proportion of the population. Depending on the severity of the CKD, drug regimens, including those for glycemic control, and dietary intake may require adjustments . Aggressive identification and treatment of risk factors for cardiovascular disease as well as complications of CKD are recommended given the very high risk of adverse cardiovascular events in patients with both diabetes and CKD.. Comments: Chronic kidney disease (CKD) is common and can be found in up to 23% of patients with diabetes.The recommended hemoglobin A1c goal for these patients is also