Nephrology — Short Cases

9 Nephrology—Short Cases Sydney Chi-Wai Tang, Kar-Neng Lai, Desmond Yat-Hin Yap, Cindy Bo-Ying Choy, and Daniel Tak-Mao Chan Overview * Usual patients: patients with chronic kidney disease, patients with active lupus, patients on haemodialysis or continuous ambulatory peritoneal dialysis, patients with renal transplanta- tion, and patients with autosomal dominant polycystic kidney disease * Go through the usual general examination (unless stated other- wise), and the usual routine of checking pulses, blood pressure, jugular venous pressure, and pallor. General * Look for uraemic complexion. * Ankle, periorbital and sacral oedema * Uraemic odour (foetor) * Vasculitic skin lesions or butterfly rash of lupus * Gouty tophi Signs of dehydration * Acidotic breathing (Kussmaul) Scratch marks due to uraemic pruritus Ecchymoses related to abnormal platelet function White bands and ridges in the nails indicating significant protein -malnutrition that could be related to urinary protein loss or poor nutritional status

118 Problem-Based Medical Case Management Band keratopathy due to chronic hypercalcaemia detected by slit-lamp examination Optic fundoscopy for hypertensive and/or diabetic changes in the retina Specific Look for arteriovenous fistula or vein grafts in patients receiv- ing haemodialysis Abdominal scars for insertion of peritoneal catheter for perito- neal dialysis Ballotable kidneys in autosomal dominant polycystic kidney disease or single ballotable kidney in obstructive hydronephro- sis or renal tumour Renal bruit, particularly in hypertensive subjects Finger prick scars or peripheral vascular disease in diabetic subjects Allograft bruit, particularly when suspecting transplant renal artery stenosis Palpable liver in patients with polycystic liver disease (associ- ated with autosomal dominant polycystic kidney disease) Percussion for bladder distention when an outflow tract obstruc- tion is suspected Rectal examination (ask permission) to assess prostatic size and consistency and gynaecological examination to exclude gynae- cologic abnormalities that may lead to obstruction (carcinoma) or persistent urinary tract infection (such as cystocele) Supplementary Pericardial rub for uraemic pericarditis Chest examination for pleural effusion secondary to fluid retention Peripheral or entrapment neuropathy due to “dialysis-related amyloidosis” for patients with longstanding renal failure or dialysis patients who have been under-dialyzed

Case 9.1 Nephrology 119 Urinalysis Dipstick for rapid detection of protein, sugar, and blood Urine specific gravity as a convenient index of urine concentration Urine pH for patients suspected of renal tubular acidosis 24-hour urine for determination of creatinine clearance and measurement of proteinuria if dipstick is positive for protein Spot urine for protein-to-creatinine ratio Urinary sediments best examined with phase contrast microscopy: — Dysmorphic or normal red cells White cells — Hyaline casts and cellular casts Crystals Bacteria I 9.1 Anti-neutrophil cytoplasmic antibodies (ANCA) positive renal vasculitis (with skin vasculitis) Classical signs Fever Bilateral cutaneous ulcers of lower limbs Look for uraemic features Kidneys not ballotable Urine albustix 3+ with large amount of red cells Causes Wegener’s granulomatosis Churg-Strauss syndrome Polyarteritis nodosa or microscopic polyangiitis

120 Problem-Based Medical Case Management Case 9.1 Important investigations Renal function test, absence of rheumatoid factor, anti-nuclear factor Skin biopsy Renal biopsy (crescentic glomerulonephritis) Discussion What is the diagnosis and which serologic tests may be confirmatory? Rapidly progressive glomerulonephritis due to renal vasculitis with skin vasculitis. Anti-neutrophil cytoplasmic antibod- ies against myeloperoxidase (p-ANCA) may occur in most patients with microscopic polyangiitis and proteinase 3 (c-ANCA) in most patients with Wegener’s granulomatosis. These are helpful but both clinical and serological overlap exists. What do the leg ulcers represent? Small vessel vasculitis. What abnormality is seen on the renal biopsy specimen? Crescentic glomerulonephritis. There is typically little or no glomerular staining for immunoglobulin by immunofluores- cence or electron microscopy; hence this condition is also known as “pauci-immune” crescentic nephritis. What pulmonary complication may occur? Pulmonary haemorrhage. What systemic disorders may be present? Microscopic polyangiitis, Wegener’s granulomatosis, or Churg-Strauss syndrome. If there are midline upper respira- tory symptoms, the clinical diagnosis is more likely Wegener’s granulomatosis. Renal involvement is less frequent in Churg- Strauss syndrome. What is the mainstay of treatment? Initial treatment usually consists of high-dose corticosteroids and cyclophosphamide or rituximab (anti-CD20). Plasmapheresis

Case 9.2 Nephrology 121 should be considered in patients with life-threatening organ involvements (e.g., pulmonary haemorrhage) or severe renal dysfunction. Maintenance treatment usually includes low-dose corticosteroid plus azathioprine or mycophenolic acid. Pitfalls and tips + The presence of leg ulcers may signify an underlying systemic vasculitic process with multi-organ involvement. + Need to watch out for potentially life-threatening complications such as acute renal failure and pulmonary haemorrhage. + Diagnosis must be made rapidly with serologic and histologic approaches. * Systemic immunosuppression must be implemented promptly to avoid irreversible organ damage. 9.2 Polycystic kidney disease Classical signs * Uraemic complexion * Urine albustix * Jarge amount of red cells * Hypertension * Bilateral ballotable kidneys * Hepatomegaly Discussion * What is the underlying renal disease and which chromo- some is commonly affected? Polycystic kidney disease, chromosome 16 (autosomal dominant). * Why is magnetic resonance imaging used instead of CT scanning used for diagnosis in this patient? Avoid contrast nephropathy in chronic kidney disease.

122 Problem-Based Medical Case Management Case 9.3 What associated condition can be seen from magnetic reso- nance imaging of the abdomen? Polycystic liver. What potential neurological complication may occur? Subarachnoid haemorrhage due to ruptured berry aneurysm. Pitfalls and tips Be sure to look for hepatomegaly due to associated polycystic liver. One kidney may be removed previously due to complications, hence it is important to look for scar of previous nephrectomy. 9.3 Transplant kidney Classical signs Look for complications: Cushingoid facies, infections Tenckhoff catheter in-situ (or abdominal scars if catheter was removed) Arteriovenous fistula in-situ Graft kidney in iliac fossa Urine dipstix for albuminuria Discussion This patient presented with fever and malaise for 3 days. What are the causes? — Bacterial infection, e.g., urinary tract infection of the graft kidney or the native kidneys, peritonitis, chest infection. — Viral infection, e.g., cytomegalovirus disease. — Acute rejection. What factors may contribute to deterioration of renal function? — Infection (bacterial or viral, e.g., BK virus). — Urine outflow obstruction (ureteric or urethral).

Case 9.3 Nephrology 123 Acute rejection of the graft kidney. Impaired arterial supply (e.g., transplant artery stenosis). Leakage of urine (urinoma) or accumulation of lymph (lymphocoele). Calcineurin inhibitor (CNI) nephrotoxicity. Nephrotoxicity due to other medications (e.g., NSAIDs, drug-associated interstitial nephritis; herbal preparations, e.g., aristolochic acid). + What investigations should be done? Septic work up: urinalysis and culture, peritoneal fluid for microscopy and culture, blood culture, sputum for culture. Blood for complete blood count, renal function and liver function tests, glucose level, cyclosporine A level, cytomeg- alovirus antigen titre. Radiological imaging: chest X-ray for infection, Doppler ultrasound of graft kidney for obstruction and renal blood flow, ultrasound of the liver and biliary system. Renal biopsy if sepsis and cyclosporine drug toxicity excluded. * What are the potential side effects of the immunosuppres- sive agents? Prednisolone: immunosuppression, Cushingoid facies, acne, mood alteration, increased appetite, diabetes mellitus, cata- ract, osteoporosis, hypertension. Cyclosporine A: immunosuppression, nephrotoxicity includ- ing both acute toxicity due to high drug level and chronic nephrotoxicity, hypertension, hyperlipidaemia, hypertricho- sis, gingival hyperplasia, lymphoproliferative disorder. Tacrolimus: acute and chronic nephrotoxicity, hand tremor, diabetes mellitus. Azathioprine: immunosuppression, dose-related myelosup- pression (caution with allopurinol), alopecia, hepatitis. Mycophenolic acid: immunosuppression (opportunistic infections); myelosuppression (cytopaenias), gastrointesti- nal disturbance (e.g., diarrhoea). mTOR inhibitors: aphthous ulcers, myelosuppression, hyperlipidemia, and rarely interstitial pneumonitis.

124 Problem-Based Medical Case Management Case 9.3 « What are the different modes of renal replacement therapy? — Peritoneal dialysis, haemodialysis, renal transplantation. o What factors should be considered before putting the patient on renal transplant waiting list? — Primary disease leading to end-stage renal failure: balance the risk of recurrence and the benefit of renal transplanta- tion; e.g., it is necessary to ensure patient’s lupus is inactive before putting the patient on transplant waiting list. — Concomitant medical illness: any concomitant medical con- ditions such as coronary arterial disease should be dealt with before renal transplantation. — Evidence of uncontrolled infection (e.g., TB) or malignancy. — Psychological status: whether the patient is psychologically prepared for the transplant operation, the potential com- plications and the need for long-term immunosuppressive medications. Drug non-compliance can lead to rejection and graft loss. Pitfalls and tips » Susceptibility to infection from over-immunosuppression » Acute rejection from under immunosuppression: exclude drug non-compliance, or drug interaction with Cyclosporine A/ Tacrolimus (metabolized via cytochrome P-450). » Need to exclude obstruction and urinary tract infection before renal biopsy

Examination case Nephrology 125 Examination case scenarios i. This patient complained of malaise. Examine her abdomen. (Transplanted kidney) Important signs » Middle-aged woman with café-au-lait complexion e Arteriovenous fistula or graft; or haemodialysis catheter (commonly internal jugular vein) e Parathyroidectomy scar on the neck « Signs related to cyclosporin A usage (e.g., gingival hyperplasia, hirsutism) « Oblique left lower abdominal scar; sometimes old Tenckhoff scars ¢ Oval dull mass in left or right lower quadrant of abdomen Diagnosis Transplant kidney for end stage renal disease (graft failure) Questions What are the common causes of end stage renal failure in this age? « Diabetic nephropathy, hypertensive nephrosclerosis, lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis. Pitfalls and tips » Do not miss Cushing’s features, fungal infection, parathyroidectomy, and nephrectomy scars.

126 Problem-Based Medical Case Management Examination case ii. Examine the abdomen (polycystic liver and kidney disease on peritoneal dialysis). Important signs . Uraemic features Tenckhoff catheter Fluid inside the peritoneal cavity Hepatomegaly with nodular surface Bilateral ballotable kidneys Diagnosis Polycystic kidney disease on peritoneal dialysis Pitfalls and tips . Do not miss the liver.