End-stage renal disease in Indo-Asians in the North-West of England.

BACKGROUND: The incidence of end-stage renal disease (ESRD) in England is increasing. There is a higher incidence of ESRD in British Indo-Asians than in the White population. AIM: To determine to what degree the increasing demand for renal replacement therapy in the UK is due to Indo-Asian patients. To study the presentation to renal services of Indo-Asian patients with ESRD and report any inequalities in initial treatment of Indo-Asian patients with ESRD compared to their White counterparts. DESIGN: Prospective, inception cohort study. METHODS: Consecutive adult patients with ESRD who started renal replacement therapy between 1 April 2000 and 31 December 2001 in all 14 renal units serving an area from North Cheshire to South Cumbria, including Greater Manchester and Lancashire, were recruited and interviewed. RESULTS: Of the 578 patients, 9.5% were Indo-Asian. The annual acceptance rate for renal replacement therapy was 342 per million population in Indo-Asians, compared with 91 per million population in the White population ( p < 0.001). Indo-Asian patients with ESRD were younger (median age 51 years vs. 60 yrs, p = 0.006) and more socially deprived (81% vs. 36.5% in the 5th Carstairs quintile, p < 0.001). A greater proportion of Indo-Asian patients with ESRD presented late to specialist renal services (31% vs. 19%, p = 0.03). Once adjusting for their younger age, atherosclerotic renovascular disease and/or hypertensive nephropathy was more prevalent in Indo-Asian patients (OR 4.9; p = 0.03). There was no difference in the initial mode of maintenance dialysis or the perception of choice the patients felt they had, based on their ethnicity. DISCUSSION: There is a silent epidemic of ESRD in Indo-Asian patients in the North-West, possibly vascular in aetiology, in which specialist intervention is late. This suggests that Indo-Asian patients should be prioritized for early intervention strategies to reduce the burden of ESRD.

Side-effects of antituberculosis drug treatment in patients with chronic renal failure.

Patients with chronic renal failure (CRF) have a high incidence of tuberculosis (TB). Those from the Indian subcontinent are at particular risk. The frequency of side-effects associated with antituberculous treatment in a group of patients with CRF was studied. All cases of TB in patients with CRF occurring over a 13-yr period at the Manchester Royal Infirmary, from 1986-1999, were identified by diagnostic coding, microbiology records and a TB database. The case notes were then reviewed. Twenty-four cases were identified, eight predialysis and 16 requiring regular dialysis. TB occurring in the dialysis group was extrapulmonary in every case. Nineteen of 24 (79%) patients were of Indian subcontinent origin and 14 of 16 (87%) dialysis patients were non-Caucasian. Adverse effects of treatment occurred in two of eight (25%) in the predialysis group and nine of 16 (56%) of the dialysis group. These were most commonly neuropsychiatric (6), hepatic (4) and gastrointestinal (4). Neuropsychiatric symptoms occurred exclusively in dialysis patients. In conclusion, a high incidence of side-effects from antituberculous medication, especially neuropsychiatric, hepatic and gastrointestinal, was identified in patients with chronic renal failure. Careful monitoring for side-effects is essential in this group, and consideration should be given to administering antituberculous chemoprophylaxis to all high-risk groups.

Blood glucose overestimation in diabetic patients on continuous ambulatory peritoneal dialysis for end-stage renal disease.

AIMS: Diabetic patients on continuous ambulatory peritoneal dialysis (CAPD) for renal failure depend on glucose analysers for regular monitoring of glycaemic control. We aim to inform health professionals of the potentially dangerous overestimation of blood glucose values by some analysers in patients using Icodextrin for dialysis. METHODS: Twenty-five patients on continuous ambulatory peritoneal dialysis (10 patients on an 8-12-h nocturnal exchange of Icodextrin) had random glucose analysis performed on venous blood using standardized reference laboratory (lab) technique (glucose oxidase GOD-PAP), and simultaneously on capillary blood using the Precision Q.I.D System (glucose oxidase method) and the Advantage meter (glucose dehydrogenase method). RESULTS: The Precision Q.I.D System agreed with the lab results in both the Icodextrin group and the non-Icodextrin group (80-90% of values fell within 20% of the corresponding lab result). In contrast, the Advantage meter agreed with the lab results only in the non-Icodextrin group (95% of values within 20% of the corresponding lab value), and not in the Icodextrin group, where only 5% of the analyser values fell within 20% of the corresponding lab value. CONCLUSIONS: The Precision Q.I.D System, which utilizes glucose oxidase reaction, is safe for use in diabetic patients treated with Icodextrin. All analysers must be cross-checked with the laboratory reference method before use in these patients.

Natural history and prognostic factors of diabetic nephropathy in type 2 diabetes.

BACKGROUND: The causes and mechanisms of increased mortality of patients with diabetic nephropathy are unclear, and its natural history is poorly understood. AIM: To evaluate risk factors for mortality in type 2 diabetic patients with nephropathy. DESIGN: Retrospective study of clinical and biochemical parameters in diabetic nephropathic patients and controls sampled from a secondary care register. METHODS: We studied 170 type 2 diabetic patients (from 1987 to 1995) with nephropathy (proteinuria >0.5 g/24 h) and 170 non-nephropathic patients. Follow-up was until death or December 1997. Details of demographics, clinical and treatment history were obtained from medical records. RESULTS: Mean follow-up was 5.3 years. Of the patients with nephropathy at baseline, 63 (37%) died compared with 14 (8%) non-nephropathic patients (chi(2)=53.8, p<0.0001). Age- and sex-adjusted all-cause mortality rates were 8.1 (6.4, 9.8) and 1.4 (0.5, 2.2) deaths per 100 person-years, respectively (rate ratio 5.8). Forty-four patients (57%) died from cardiovascular causes (rate ratio 5.4). Mortality was directly proportional to degree of proteinuria: 0.5-2 g/24 h, 4.6 (2.9-7.1); >2 g/24 h, 9.9 (7.3-13.5) per 100 patient-years. A 36% (5-78%) excess risk of mortality was observed for each log unit increase in proteinuria. Multivariate Cox regression analyses confirmed a five-fold excess risk for all-cause and cardiovascular mortality in patients with nephropathy compared with those without. This was independent of other risk factors including baseline age [5% (1-8%)/year], creatinine [2.5 (1.12-5.6)/10 micromol/l] and glycaemic control (HbA(1c)) [15% (1-31%) per 1% rise]. CONCLUSIONS: Proteinuria is a potentially preventable and reversible risk factor associated with high mortality in type 2 diabetic patients. Prevention of the development of overt nephropathy and improvement in diabetes control may reduce mortality in these patients.

Association of sex hormone status with the bone loss of renal transplant patients.

BACKGROUND: Bone loss is an important problem in renal transplantation recipients. The role of sex hormones in this setting has not been previously addressed. The objective was to investigate whether sex hormone status is associated with bone mass loss in renal transplant recipients. METHODS: Thirty patients (16 men and 14 women, of which eight were post-menopausal) were studied by bone densitometry and bone biopsy. In women, serum oestradiol levels and menopausal status were determined; in men, serum testosterone levels were assessed. RESULTS: Mean age was 48+/-11 years. Time on dialysis was 13+/-17 months, and time since transplantation was 125+/-67 months. Thirteen patients were on cyclosporine A (CsA) monotherapy, 12 on azathioprine plus prednisolone (PRED) dual therapy, and five on CsA, azathioprine and PRED triple therapy. In men, serum testosterone levels were 19.7+/-6.8 nmol/l (mean+/-SD). In pre-menopausal women, oestradiol serum levels were 209(128-289) pmol/l (median (percentiles 25-75%)), and in post-menopausal women 93(54-299) pmol/l (non-significant). Univariate analysis in women demonstrated that serum oestradiol levels were positively correlated with Z scores of osteoblast surface (r=0.70, P=0.005), osteoid surface (r=0.75, P=0.002) and trabecular wall thickness (r=0.68, P=0.008). In men, a weak correlation was seen between serum testosterone levels and the cumulative dose of PRED (r=-0.52, P=0.06). In the multivariate analysis, two models of multiple regression were employed (one for women and one for men), considering the densitometric and histomorphometric variables (Z scores) as dependent variables. Serum testosterone in men did not predict any of the densitometric nor histomorphometric variables analysed, while serum oestradiol in women was an independent predictor for the osteoblast surface (r=0.81, P=0.003), osteoid surface (r=0.82, P=0.009) and trabecular wall thickness (r=0.54, P=0.05). CONCLUSIONS: In female renal transplant recipients, serum oestradiol levels independently predict the bone status, while in men, factors other than testosterone seem to influence bone loss. Our results give rise to the hypothesis that sex hormone replacement therapy may play a role in prevention and/or treatment of the bone loss in women following renal transplantation.

Peritoneal tuberculosis in patients receiving continuous ambulatory peritoneal dialysis.

BACKGROUND: Patients with chronic renal failure have an increased risk of tuberculosis (TB). This occurs with much higher frequency within the first 12 months of initiating dialysis and is usually extrapulmonary in nature. Patients most at risk are those from susceptible ethnic groups, especially the Indian subcontinent. Peritoneal TB, otherwise relatively uncommon, has emerged as an important form of TB in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: All cases of peritoneal TB occurring at our institution in patients undergoing CAPD over a 13 year period were identified and analysed. RESULTS: Eight cases were identified, of which seven were non-Caucasian. These patients' characteristics and outcomes are presented. All were undergoing CAPD and most developed TB within 12 months of initiating dialysis. All presented with fever, but symptoms and signs were indistinguishable from bacterial peritonitis. Six were culture-positive, mainly from peritoneal dialysis fluid, but only two cases proved smear-positive. All were treated with standard anti-tuberculous chemotherapy. Three went on to permanent haemodialysis as a result of peritonitis and three have died, one of these as a result of TB. CONCLUSIONS: Peritoneal TB, whilst otherwise relatively uncommon, is an important manifestation of TB in CAPD patients and usually develops soon after commencing dialysis. The reasons for this are unknown and require further research.

Newer peritoneal dialysis solutions.

Currently available peritoneal dialysis (PD) solutions provide for adequate removal of metabolic waste and manage fluid and electrolyte imbalances. They are, however, bioincompatible and do lead to peritoneal membrane changes with long-term use. Glucose is now strongly implicated in this. Newer solutions (icodextrin, bicarbonate, those with reduced glucose degradation products, amino acids) provide for greater biocompatibility and also address the question of fluid removal and retention. The future of PD solutions lies in combinations and additives.

Peritoneal dialysis. Prevention and control of infection.

In spite of the reduction in peritonitis and catheter-related infection rates in patients undergoing peritoneal dialysis, these infections remain major sources of morbidity and transfer to haemodialysis. Touch contamination at the time of doing the exchanges is still a major cause of peritonitis and leads to Gram-positive organisms (coagulation-negative staphylococcus) being the most common pathogens. Newer exchange techniques have reduced this incidence but the more serious pathogens (Staphylococcal aureus, pseudomonas and fungi) remain a major problem. Treatment has to be immediate, and hence empirical, giving adequate cover for both Gram-positive and Gram-negative organisms. The use of vancomycin as an initial antibacterial has been discontinued because of the problem of vancomycin-resistant enterococcus. Recent guidelines advocate the use of a first generation cephalosporin combined with ceftazidime (if the urine output is >100 ml/day) or an aminoglycoside in anuric patients. Subsequent therapy changes are made upon bacterial isolation and sensitivities. Vancomycin is reserved for methicillin-resistant staphylococcus. Peritoneal catheter-related infections (exit site and tunnel) are predominantly caused by S. aureus and pseudomonal organisms and can be difficult to eradicate. Tunnel infections invariably involve the catheter dacron cuffs and therefore are more likely to lead to peritonitis; in this situation catheter removal is the treatment of choice. Treatment of exit-site infections is with oral antibacterials (penicillinase-resistant penicillins, cefalexin). Vancomycin is avoided if possible. The identification that nasal carriage of S. aureus predisposes to exit-site and tunnel infections has led to prophylactic regimens to combat this problem. Mupirocin applied at the exit site leads to a reduction in catheter-related infections and peritonitis.

Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure.

BACKGROUND: Resistance to the action of parathyroid hormone (PTH) has been demonstrated in end-stage renal failure and is considered to be important in the pathogenesis of secondary hyperparathyroidism. The mechanism of resistance is unknown. However, altered regulation of cellular PTH/PTH-related protein (PTH/PTHrP) receptor (PTH1R) has been assumed to be important. METHODS: We have used in situ hybridization to examine PTH1R mRNA expression by osteoblasts in human bone and have compared the expression in high- and low-turnover renal bone disease, high-turnover nonrenal bone disease (healing fracture callus and Pagetic bone), and normal bone. Bone biopsies were formalin fixed, ethylenediaminetetraacetic acid decalcified, and paraffin wax embedded. A 1.8 kb PTH1R cDNA probe, labeled with 35S, was used, and the hybridization signal was revealed by autoradiography. The density of signal over osteoblasts was quantitated using a semiautomated Leica image analysis software package. RESULTS: The mean density of PTH1R mRNA signal over osteoblasts in renal high-turnover bone was only 36% of that found in nonrenal high-turnover bone (P < 0.05) and 51% of that found in normal bone (P < 0.05). Osteoblast PTH1R mRNA signal in adynamic bone from individuals with diabetes mellitus was 28% of normal bone (P < 0.05) and 54% of that found in renal high-turnover bone (P < 0.05). CONCLUSIONS: These results demonstrate a down-regulation of osteoblast PTH1R mRNA in end-stage renal failure in comparison to normal and high-turnover bone from otherwise healthy individuals, and provide an insight into the mechanisms of "skeletal resistance" to the actions of PTH.

Effect of 1,25-dihydroxyvitamin D3 and calcium carbonate on bone loss associated with long-term renal transplantation.

To investigate the effect of calcitriol plus calcium carbonate on the bone loss associated with long-term renal transplantation, 30 patients with serum creatinine levels less than 2.0 mg/dL were randomly allocated to a control (n = 14) or treatment group (n = 16) and studied with bone biopsy and densitometry at baseline and after 1 year of follow-up. Calcitriol (0.25 microg/d) plus calcium carbonate (500 mg/d of elemental calcium) were administered to patients in the treatment group. Comparing the baseline and final data of each group at a time, no change in bone mineral density (BMD) z score was observed at the distal radius (control, -0.8 +/- 0.8 versus -0.6 +/- 0.9; treatment, -1.0 +/- 1.0 versus -1.0 +/- 1.1). However, a significant increase (P < 0.05) was found at the lumbar spine in both groups (control, 0.1 +/- 1.6 versus 0.4 +/- 1.6; treatment, -0.1 +/- 1.5 versus 0.3 +/- 1.5) and only in the treatment group at the femoral neck (control, -0.9 +/- 1.0 versus -0.8 +/- 1.0; treatment, -0.5 +/- 0.9 versus -0.3 +/- 1.1). When BMD was compared between groups, no significant differences were observed at the evaluated anatomic sites at baseline or after 1 year of follow-up. After 1 year of follow-up, adjusting for age and sex (z score), the control group showed a trend to reduce the value of several histomorphometric parameters, including osteoblast surface (-2.2 +/- 6.1 versus -3.4 +/- 3.9), osteoid surface (-2.3 +/- 3.5 versus -3.1 +/- 3.9), and osteoclast surface (0.2 +/- 5.0 versus -1.3 +/- 3.3). Consequently, there was a significant reduction (P < 0.05) in mineralizing surface (-9.8 +/- 11.0 versus -15.8 +/- 12.3) and appositional rate (-5.8 +/- 2.7 versus -7.6 +/- 2.2). In the treatment group, a significant reduction (P < 0.05) in osteoclast surface was observed at the end of the study (3.9 +/- 6.8 versus -1.2 +/- 4.1), and although a trend to reduce osteoblast surface (-2.5 +/- 2.6 versus -3.2 +/- 5.7) and osteoid surface (-2.1 +/- 2.5 versus -3.2 +/- 2.8) was also found, patients maintained approximately the same level of wall thickness (-5.2 +/- 5.3 versus -5.3 +/- 3.3) and bone volume (-2.7 +/- 1.8 versus -2.5 +/- 1.7). However, there was no improvement in mineralizing surface (-4.2 +/- 2.9 versus -10.4 +/- 3.6) or appositional rate (-5.8 +/- 3.1 versus -8.1 +/- 2.6). No significant differences in bone histomorphometric variables were observed between groups after 1 year of follow-up. In conclusion, 1,25-dihydroxyvitamin D3 and calcium carbonate did not significantly improve bone loss in long-term renal transplant recipients. However, significant osteoclast suppression and a trend to maintain trabecular bone volume and wall thickness as well as improve the axial BMD were observed in the treatment group.

Outcome of pregnancy following renal transplantation.

Fertility is restored following renal transplantation, and the potential for motherhood can be realised. This retrospective study reviews the outcome of 53 pregnancies, in 24 patients, between 1988 and 1995. All patients underwent transplant surgery, and received antenatal care at a single centre. The mean age at first conception was 27.6 years, and graft function, as assessed by serum creatinine at the time of antenatal booking, was good. Patients were referred early, seen regularly, and had both obstetrician and nephrologist involved in management. The main maternal complication was hypertension, affecting 50% of patients. Seven patients had a worsening of pre-existing hypertension, whilst four patients developed hypertension for the first time during pregnancy. Graft function was, for the most part, well maintained. Four patients required delivery because of declining renal function, two of these went on to develop frank rejection, necessitating a return to dialysis within 3 months of delivery. These figures however are not higher than have been reported in the non-pregnant population. The overall pregnancy loss was 26%. There were a total of 39 live births. Premature birth was higher than that of the general population, with 57% of infants in the study delivering before 37 weeks' gestation (average 34 weeks' gestation) Of the 39 infants born alive 27% were growth retarded. Congenital abnormalities were, reassuringly, no higher than that in the general population, despite the need to take immunosuppressive drugs. Delivery was by caesarean section in 64% of cases, which may reflect a high degree of clinical caution in this group of patients. The study concludes that, whilst risks are recognised, for both the mother and infant, with a careful, multidisciplinary approach, the outcome is generally good.

A review of food provision to a renal ward and the proposed appointment of feeding assistants.

Malnutrition among renal patients has been widely documented and is associated with increased morbidity and mortality. Advances in dialysis technology and transplantation have helped to increase patient long-term survival, and as more elderly patients commence dialysis programs, the problem of malnutrition is escalating. Hospitalized renal patients are at a greater risk, as dietary intakes may be reduced for a number of reasons. A multidisciplinary team decided to review the existing cook-chill plated meal system and all food provision to the renal ward. The aim of this review was to assess the nutritional intake of renal inpatients and to gauge patients' and relatives' attitudes towards hospital food provision. From these results, we hoped to go on and implement some changes to help improve the situation. Results showed that 34% of the patients ate half or less of the hospital food provided, and 80% of patients surveyed relied on food brought in by relatives and friends. Actual dietary intakes were compared to Dietary Reference Values (DRVs; Department of Health [DoH], UK, 1995). One hundred percent of the patients did not achieve the DRVs for energy, iron, potassium, zinc, folate, B6, and riboflavin. Sixty-six percent of the patients did not achieve the DRV for protein. These results were discussed by the multidisciplinary group, and it was decided to trial a cook-chill bulk trolley to replace the existing plated meal system. Unfortunately, to implement a bulk trolley system, the ward needs someone to serve the food. This could be the job of a "feeding assistant" or "ward hostess." A bid has been put forward to the hospital Trust Board to obtain funding for these "feeding assistants, " and the bulk trolley can be acquired from existing funds. It is hoped that the creation of these new posts will go some of the way towards improving the patients' dietary intake while in the hospital.