Omeprazole-induced acute interstitial nephritis is not related to CYP2C19 genotype or CYP2C19 phenotype.

AIM: Omeprazole-induced acute interstitial nephritis (OIAIN) is a rare adverse event. It is unknown if this is an idiosyncratic immune mediated reaction or if it relates to direct drug toxicity. Individuals who are homozygous for the variant alleles of CYP2C19 are poor metabolizers of omeprazole and have a greater exposure to the drug. The aim of this study was to determine the prevalence of the CYP2C19 poor metabolizer genotype and phenotype in patients with OIAIN. METHODS: Twenty patients were genotyped for the CYP2C19 variant alleles (2, 681G>A and 3, 636G>A) by RFLP-PCR analysis and eighteen phenotyped for CYP2C19 metabolizer status. RESULTS: The frequency of the CYP2C19 2 allelic variant was 12.5%, no 3 allelic variants were detected and no patient was a homozygous variant genotype. This was not different from the expected frequency. 33% of subjects were phenotypically CYP2C19 poor metabolizers. CONCLUSIONS: There was discordance between CYP2C19 genotype and phenotype. However, up to 45% of healthy elderly subjects have a poor metabolizer phenotype. Thus neither CYP2C19 poor metabolizer genotype nor phenotype is a risk factor for OIAIN.

Gout in solid organ transplantation: a challenging clinical problem.

Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor. Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined. Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with renal failure, solid organ transplant or tophaceous/polyarticular gout. Monitoring for hepatotoxicty is essential for patients taking benzbromarone. Physicians should carefully consider therapeutic options for the management of hypertension and hyperlipidaemia, which are common in transplant recipients. While loop and thiazide diuretics increase serum urate, amlodipine and losartan have the same antihypertensive effect with the additional benefit of lowering serum urate. Atorvastatin, but not simvastatin, may lower uric acid, and while fenofibrate may reduce serum urate it has been associated with a decline in renal function. Gout in solid organ transplantation is an increasing and challenging clinical problem; it impacts adversely on patients' quality of life. Recognition and, if possible, alleviation of risk factors, prompt treatment of acute attacks and early introduction of hypouricaemic therapy with careful monitoring are the keys to successful management.

Henoch-Schönlein purpura in a renal transplant recipient with prior IgA nephropathy following influenza vaccination.

Henoch-Schönlein purpura (HSP) is a systemic small-vessel leucocytoclastic vasculitis with deposition of immune complexes containing Immunoglobulin A (IgA). IgA Nephropathy (IgAN) is a glomerulonephritis caused by mesangial deposition of IgA. The onset of HSP, but not IgAN, has been linked to influenza vaccination. We report the first case of HSP with glomerular involvement, in a renal transplant recipient following influenza vaccination. The patient had prior end-stage renal failure (ESRF) secondary to IgAN, without clinical evidence of IgAN recurrence after transplantation. This is of clinical relevance as influenza vaccination is regarded safe, effective, and recommended after renal transplantation. Nephrologists should be aware of the potential for influenza vaccination to have adverse effects in renal transplant recipients, especially if the primary renal disease is HSP or IgAN.

IgA nephropathy in identical twins: an excellent donor and recipient outcome 11 years after transplantation.

We present a case of IgA nephropathy (IgAN) in monozygotic twins with excellent donor and recipient outcome 11 years after transplantation. The recipient developed IgAN at 26 years and progressed to end-stage renal failure 10 years later. His identical twin who had hypertension, intermittent microscopic haematuria and positive IgA immunofluorescence on biopsy became his donor. Eleven years following transplant, in the absence of immunosuppression, the recipient has stable graft function [estimated glomerular filtration rate (eGFR) 47 mL/min/1.73 m(2), Modification of Diet in Renal Disease (MDRD)], controlled hypertension on two medications and minor microscopic haematuria. The donor has good renal function (eGFR 51 mL/min/1.73 m(2), MDRD), controlled hypertension on one medication and normal urine.

Rhabdomyolysis following laparoscopic radical nephrectomy: a case to heighten awareness.

Rhabdomyolysis, myoglobinuria and acute renal failure are rare complication of surgery. Long operative time, increased body mass, lateral decubitus positioning and extracellular volume depletion may predispose to this condition. The authors describe the case of a 70-year-old man with renal cell carcinoma who underwent a laparoscopic right radical nephrectomy in the lateral decubitus position. His postoperative course was complicated by acute renal failure due to rhabdomyolysis. Heightened awareness, early recognition and treatment of this condition are important, particularly as laparoscopic nephrectomy is becoming a common procedure for living donor transplantation.

Gout in renal transplant recipients.

AIMS: The aims of the present audit were to determine the prevalence of gout in renal transplant recipients in Canterbury, New Zealand, to identify risk factors for gout, and to assess the range of treatments used, their efficacy and complications. In addition, the authors wished to assess the impact of post-renal transplant gout on the patient. METHODS: Patients with post-transplantation gout were identified from the Christchurch Hospital Nephrology database. For each patient with gout a post-renal transplantation recipient without gout post transplant was found matched for age, sex and date of transplant. Case notes were audited and patients interviewed. RESULTS: In total, 47/202 (23%) living renal transplant recipients had gout post transplant. Those patients with gout were more likely to be taking a loop diuretic (68%vs 34%, P < 0.001), to have a higher serum urate and impaired renal function and to have had gout prior to the transplant. Of those patients who developed gout post transplant 70% had an attack at least every 3 months. Of those who returned to work post transplant 48% required time off work because of gout. CONCLUSION: out is an important problem in the post-transplant population causing significant morbidity and time off work. Diuretics, impaired renal function, gout prior to transplantation and hyperuricaemia are important risk factors. The need for diuretic therapy should be kept under review in these patients. Hypouricaemic therapy should be considered early in those who develop gout post renal transplantation. Further studies are required to determine whether treatment for asymptomatic hyperuricaemia is justified.

Older patients in the nephrology clinic--should they be referred?

AIM: To review the outcomes of elderly patients referred to a nephrology clinic and to develop referral guidelines. METHODS: A retrospective audit of patients aged 65 years or older referred over a 24-month period to a nephrology clinic. Outcomes assessed were whether a renal diagnosis was made and if there was any change in management. RESULTS: Sixty-one patients were referred with an average age of 74 years (range 65-88 years). The commonest reason for referral was renal impairment (69%); mean estimated creatinine clearance 32 ml/min. Diagnoses included hypertensive renal disease (30%), chronic renal failure - cause unknown (18%) and diabetic nephropathy (8%). In the majority of cases, the diagnosis was clinical. Renal biopsy was performed on four patients and declined by a further two. Management usually consisted of advice regarding clinical monitoring and drug treatment (80%). The clinic visit resulted in a change of management in 50% of cases. CONCLUSIONS: Most elderly patients with renal disease have chronic pathology for which intensive investigation is not warranted. The majority of nephrology clinic referrals resulted in advice on clinical management being given to the general practitioner. Patients with severe or acute renal impairment are more likely to be investigated and offered treatment. Referral guidelines for general practitioners may aid appropriate referral.