John Walls

Increased incidence of end-stage renal failure secondary to diabetes mellitus in Asian ethnic groups in the United Kingdom.

Diabetic renal disease is more common in patients of Asian ethnic origin than White Caucasians in the United Kingdom. This study determines whether a disparity in the incidence of end‐stage renal failure secondary to diabetes mellitus exists between these ethnic groups. The incidence of treated end‐stage renal failure was estimated using the person‐time at risk incidence rate for patients receiving renal replacement therapy secondary to diabetes mellitus in the county of Leicestershire from 1979 to 1988. The incidence rate of end‐stage renal failure expressed for the estimated population of patients with diabetes mellitus in patients of Asian ethnic origin was 486.6 (95% CI, 185.1 to 788.1) cases per million person‐years per year, compared to 35.6 (17 to 54.2) in White Caucasians. All patients of Asian ethnic origin developing end‐stage renal failure had non‐insulin‐dependent diabetes. The high incidence of end‐stage renal failure secondary to diabetes mellitus in patients of Asian ethnic origin in the UK imparts significant public health implications for resource planning and allocation, and the need to initiate strategies to ameliorate renal disease in this ethnic group.

SELECTION-ADJUSTED COMPARISON OF LIFE-EXPECTANCY OF PATIENTS ON CONTINUOUS AMBULATORY PERITONEAL DIALYSIS, HAEMODIALYSIS, AND RENAL TRANSPLANTATION

To investigate the controversy surrounding the life-expectancy of patients on continuous ambulatory peritoneal dialysis (CAPD) compared with that of patients on haemodialysis or transplantation mortality data from 389 patients accepted for renal replacement therapy in Leicester between July, 1974, and July, 1985, were retrospectively analysed with respect to a wide range of pre-treatment variables (6 scales and 115 binary variables), by a method (Coxs) that adjusts for the distorting influence of selection bias. 9 independent variables were identified as having a significant influence on survival. Adverse factors were age, amyloidosis, ischaemic heart disease, convulsions, and acute presentation. Beneficial variables were male sex, parenthood, pyelonephritis, and residence in Leicestershire. By correcting for the influence of these variables and using time-dependent treatment co-variates, the bias adjusted estimates of the relative risk of death were 1 for patients on CAPD, 1.30 for those on haemodialysis, and 1.09 for patients who received transplants. These risks do not differ significantly from one another and suggest that CAPD is at least as effective as haemodialysis or transplantation at preserving life.

Effect of Varying Quantity and Quality of Dietary Protein Intake in Experimental Renal Disease in Rats

Dietary protein restriction is known to be beneficial in the preservation of renal function when renal mass is reduced. This study investigates the effects of two different dietary proteins, casein and soya, upon renal function in normal rats and rats subjected to subtotal nephrectomy. The diets were isocaloric, with identical sodium, potassium and phosphorus contents. Normal rats ingesting a 24% soya protein diet demonstrate lower effective renal plasma flow rates and lower glomerular filtration rates than rats ingesting a 24% casein diet. Experimental animals were subjected to a unilateral nephrectomy and contralateral partial renal infarction and were fed either casein or soya, at 24 or 12% levels, for 3 months. Those animals ingesting the soya diets demonstrated improved survival (p less than 0.05), less proteinuria (p less than 0.02), less renal hypertrophy (p less than 0.005) and less renal histological damage. The nature of the dietary protein appears to influence both normal renal function and the progression of experimentally induced renal disease.

IS CHRONIC RENAL TRANSPLANT REJECTION A NON-IMMUNOLOGICAL PHENOMENON?

Five patients with chronic renal transplant rejection were subjected to dietary protein restriction (0.6 g/kg ideal body weight daily) with no change in immunosuppressive therapy. In all five patients the slope of the curve of reciprocal serum creatinine and time decreased (mean -46.0 +/- 11.8 before diet fell to -11.7 +/- 9.4; p less than 0.01). These findings support the hypothesis that non-immune mechanisms are dominant is chronic renal transplant failure.

Deterioration in renal function associated with angiotensin converting enzyme inhibitor therapy is not always reversible

Abstract. Fifteen patients presented between January 1986 and January 1991 with deterioration in renal function coincident with the introduction of angiotensin converting enzyme inhibitors. There was evidence of extrarenal vascular disease in 12 patients and preexisting renal impairment in 13. Four patients remained dialysis‐dependent and died within 4 weeks of presentation. Five patients required short‐term dialysis. Serum creatinine remained above pre‐treatment values in seven patients. Conventional explanations of the decline in renal function with ACE inhibition do not account for irreversible decrements in renal function. Possible mechanisms for this observation and clinical guidelines to identify patients at risk are suggested. We conclude that these agents should be used with great care in patients in whom atherosclerotic vascular disease is likely.

BLOOD PRESSURE AND ERYTHROPOIETIN

SIR,-We have seen a case of hypertensive encephalopathy in a patient receiving recombinant erythropoietin (EPO) which was much more severe than the cases mentioned by Dr Raine (Jan 16, p 97) in his review of the cardiovascular benefits and risks of correcting the anaemia of chronic renal failure with EPO. A 40-year-old man with nephrocalcinosis and renal tubular acidosis had been on haemodialysis for 51 years. Before starting EPO (as part of a multicentre trial) his haemoglobin concentration (Hb) had fallen to around 6 g/dl every 6 weeks, rising to 8 or 9 g/dl after transfusion. Despite a 4-year history of mild hypertension and recently diagnosed type IIb hyperlipidaemia there was no clinical evidence of cardiovascular disease. When he was put on EPO his Hb

Impaired system A amino acid transport mimics the catabolic effects of acid in L6 cells.

Background Metabolic acidaemia stimulates protein catabolism in skeletal muscle cells, leading to muscle wasting. As this occurs without decreasing cytosolic pH, the initial signal is unclear. A possible explanation is that extracellular pH acts on solute transporters at the cell surface, inhibiting nutrient influx.

The role of continuous ambulatory peritoneal dialysis in end-stage renal failure due to multiple myeloma.

A study in 10 patients (eight male, two female; mean age 61.9 +/- 10.7 years) suffering from multiple myeloma (MM) and end-stage renal failure (ESRF) is detailed. Continuous ambulatory peritoneal dialysis (CAPD) was the preferred mode of chronic dialysis in all the patients. Survival after diagnosis was 32.2 +/- 23.9 months. Survival after starting dialysis was 24.6 +/- 20.6 months. All patients on CAPD were adequately dialyzed and in good fluid control. Peritonitis was the main problem on CAPD (one episode per 5.6 patient-months). The majority of peritonitis episodes responded to intraperitoneal antibiotic therapy. One patient with Staphylococcus aureus peritonitis, septicemia, and neutropenia secondary to chemotherapy, died. Recommendations for prophylaxis and treatment of peritonitis are given. Three patients were transferred to hemodialysis. The use of subclavian vein catheters during hemodialysis was associated with a high incidence of gram-positive septicemia. Alkylating agent-based chemotherapy resulted in hematological responses in five patients. Survival after diagnosis in those responders was 47.4 +/- 25.6 months, compared with 17.0 +/- 7.2 months in the nonresponders (P less than 0.05). All responders subsequently relapsed. Four patients died with progressive myeloma. Bone marrow suppression resulted in a high blood transfusion requirement, neutropenia, and thrombocytopenia associated with bleeding into the gastrointestinal tract and central nervous system. Uremic myeloma patients can be adequately dialyzed using CAPD. Those patients who do not have an initial hematological response have a poor prognosis.

Acute renal failure associated with haematological malignancies: A review of 10 years experience

Harris KPG, Hattersley JM, Feehally J, Walls J. Acute renal failure associated with haematological malignancies: A review of 10 years experience. Eur J Haematol 1991: 47: 119–122.

Acidosis Downregulates Leptin Production from Cultured Adipocytes through a Glucose Transport-Dependent Post-transcriptional Mechanism

Metabolic acidosis, a common feature of uremia, has a well documented wasting effect on skeletal muscle. In contrast, the effect of metabolic acidosis on adipose tissue is unknown. Serum levels of the adipocyte hormone leptin have been shown to be lower in acidotic uremic rats when compared with uremic controls. This study investigated the effect of acidosis on leptin protein secretion and leptin gene expression. This was studied in vitro by means of 3T3-L1 cultured adipocytes. Leptin secretion was decreased at an acid pH of 7.1 compared with a control pH of 7.5 (1277 versus 1950 pg/well/48 h, P < 0.05). In contrast, acidosis did not affect leptin mRNA content. Glucose transport was reduced by 39% at pH 7.1 at 24 h, which was comparable in magnitude with the inhibition of leptin secretion at the same pH. The glucose transport inhibitors cytochalasin B (0.5 to 50 micro M) and phloretin (0.05 to 0.25 mM) mimicked the effect of acidosis and reduced leptin secretion in a dose-dependent fashion (P < 0.02). Dose-response curves for the inhibition of glucose uptake showed that decreasing glucose transport to the same extent as with acid was sufficient to drive down leptin secretion, independently of changes of leptin mRNA. Acid decreases leptin secretion from 3T3-L1 adipocytes through a post-transcriptional mechanism via changes in glucose transport. This starvation-like response may be physiologically important in conditions such as uremia to prevent excessive energy expenditure.