The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis.

BACKGROUND: Some studies suggest that progression of renal disease is slower in women than in men. However, other factors that are also associated with progression of renal disease have not always been taken into account. Therefore, we undertook this analysis to explore the independent association of renal disease progression with gender. METHODS: We analysed a pooled database of patients with non-diabetic renal disease enrolled in 11 randomized controlled trials evaluating the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) for slowing renal disease progression. The primary end point was the combined outcome of doubling of baseline serum creatinine or onset of end-stage renal disease (ESRD). The secondary end point was the onset of ESRD alone. We performed multivariable Cox proportional hazards analysis to study the independent effect of gender on these end points after adjusting for baseline patient characteristics, and changes from baseline to follow-up systolic blood pressure (SBP) and urine protein (UP) excretion. RESULTS: The total number of patients was 1860: 645 (35%) females and 1215 (65%) males. Mean duration of follow-up was 2.2 years. The proportions randomized to ACEI (51%), mean baseline serum creatinine (2.2 mg/dl) and mean age (52 years) were similar for both genders. Mean baseline SBP was greater in women than in men: 151 vs 147 mmHg (P < 0.001). Mean baseline UP was significantly lower in women compared with men: 1.3 vs 2.1 g/day (P < 0.001). A total of 311 (16.7%) patients developed the primary end point, and 176 (9.5%) developed the secondary end point. The unadjusted relative risk (RR) with 95% confidence interval (CI) for the primary end point in women vs men was 0.98 (0.77-1.24). It became 1.32 (1.03-1.69) after adjusting for the baseline variables and interaction between ACEIs and baseline UP, and 1.36 (1.06-1.75) after adjusting for baseline variables and changes in SBP and UP during follow-up. Similar results were found for the outcome of ESRD. CONCLUSIONS: Our findings suggest that the rate of renal disease progression may not be slower, and may even be faster in women compared with men, after adjusting for other factors associated with a faster rate of progression. We caution that most women in our database were of post-menopausal age, and thus our findings may not extend to younger women.     

Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD

Nephronophthisis (NPHP) is one of the most common genetic causes of CKD; however, the underlying genetic abnormalities have been established in <50% of patients. We performed genome-wide analysis followed by targeted resequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 associated with an NPHP-like phenotype. Furthermore, we identified four additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic GN, interstitial nephritis, or unknown etiology. Immunohistochemistry in human embryonic kidney tissue demonstrated that the expression patterns of ANKS6 change substantially during development. Furthermore, we detected increased levels of both total and active β-catenin in precystic tubuli in Han:SPRD Cy/+ rats. Overall, these data indicate the importance of ANKS6 in human kidney development and suggest a mechanism by which mutations in ANKS6 may contribute to an NPHP-like phenotype in humans.     

Biology of fibroblasts

Summary During recent years, fibroblasts have been recognized as a heterogenous cell type with a remarkable degree of differentiation and important functional properties in health and in disease. Our better understanding of the biology of fibroblasts has elucidated some of the mechanisms responsible for fibrosis of the kidney and other organs. In chronic inflammation, activation of differentiating fibroblasts and/or the selection of highly proliferative subsets results in a specialized phenotype of fibroblast, often called the myofibroblast, which is the pivotal cell in fibrogenesis and the subsequent destruction of the parenchyma. In addition, perivascular and epithelial cells may be recruited to transdifferentiate into fibroblast-like cells to joint in this process. So far, many aspects of cell regulation in fibrogenesis have been described, with most of the known regulatives being cytokines. However, further research is imperative in this interesting area to eventually overcome the fatal course of chronic fibrosis, which leaves the patient and the physician without any hope for sufficient treatment. This paper was presented at the 2nd International Forum “The Frontiers of Nephrology”, Tokyo, May 10, 1998.     

Chemokines and nephritis

Conclusion In summary, experimental and clinical studies in the last few years have shown that renal tissues produce chemokines in response to stimulation by proinflammatory cytokines, immune complexes, complement activation, vasoactive peptides, and hypoxia. These tissue insults lead to a transient increase in chemokines. This increase initiates the recruitment of inflammatory cells, and probably starts the auto-induction loop of transforming growth factor-β, which may mediate tissue fibrogenesis. The development of neutralizing humanized antibodies against chemokines or the development of nonsignaling receptor antagonists may offer therapeutic opportunities in the treatment of renal injuries or transplant rejection. This paper was presented at the 2nd International Forum “The Frontiers of Nephrology,” Tokyo May 10, 1998.     

The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.     

Acquired renal cystic disease in children prior to the start of dialysis

This report describes the clinical course and serial sonographic findings in three children who developed acquired renal cystic disease (ARCD) prior to the institution of dialysis. The children were aged from 3 years to 13 years and their estimated glomerular filtration rate varied from 8 to 13 ml/min per 1.73 m² when ARCD was diagnosed. Their primary renal disorders, which included hemolytic-uremic syndrome and focal segmental glomerulosclerosis, had been present for 1.5–11.5 years prior to the cysts being discovered. These patients show that ARCD may develop in children with chronic progressive renal parenchymal disease prior to the institution of specific therapy for end-stage renal disease.     

Extent and Severity of Coronary Disease and Mortality in Patients with End-Stage Renal Failure Evaluated for Renal Transplantation

The purpose of this study is to explore the relationship between coronary artery disease (CAD), transplantation status and subsequent mortality in end-stage renal disease (ESRD) patients undergoing evaluation for renal transplantation. Two hundred fifty-three ESRD patients at high risk for CAD underwent coronary angiography as part of a renal transplant evaluation. The cohort was divided into three groups: Group 1 (n = 127) had no vessels with ≥50% stenosis, Group 2 (n = 56) had one vessel with ≥50% stenosis and Group 3 (n = 70) had two or more vessels with ≥50% stenosis. Long-term survival was determined; median follow-up was 3.3 years. The baseline characteristics were similar except for older age and higher proportion of diabetes mellitus, dyslipidemia and peripheral vascular disease in Groups 2 and 3 patients as compared to Group 1. Survival was worse in Group 3 compared to Group 1 (p < 0.0001). Each of the three subgroups had better survival with renal transplantation than those who did not undergo transplantation (p < 0.0001). Although the degree of CAD is related to subsequent mortality, transplantation is associated with better survival regardless of the extent and severity of CAD. Thus, the presence of CAD should not exclude ESRD patients from consideration for this therapy.     

Trends in the incidence of renal replacement therapy for end-stage renal disease in Europe, 1990-1999.

BACKGROUND: The epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) varies considerably worldwide, but we have lacked reliable quantitative estimates of trends in the incidence by age, sex and cause in Europe over the last decade. METHODS: We analysed data from nine countries participating in the ERA-EDTA registry: Austria, Belgium, Denmark, Finland, Greece, The Netherlands, Norway, Spain and UK (Scotland). Adjusted incidence rates for age and sex were studied for 2 year periods between 1990 and 1999. Average annual changes (%) were estimated by Poisson regression. RESULTS: The adjusted incidence rate of RRT increased from 79.4 per million population (pmp) (range: 58.4-101.0) in 1990-1991 to 117.1 pmp (91.6-144.8) in 1998-1999, i.e. 4.8% (3.1-6.4%) each year. This increase did not flatten out at the end of the decade, except in The Netherlands, and was greater in men than women, 5.2 vs 4.0%/year. In most countries, the incidence rate remained stable for those younger than 45 years; it rose by 2.2%/year on average in the 45-64 year age group and by 7.0% among those 65-74 years; it tripled over the decade in those 75 years or older, and by 1998-1999 it ranged from 140.9 to 540.4 pmp between countries. The incidence of ESRD due to diabetes, hypertension and renal vascular disease nearly doubled over 10 years; in 1998-1999, it varied between countries from 10.2 to 39.3 pmp for diabetes, from 5.8 to 21.0 for hypertension, and from 1.0 to 15.5 for renal vascular disease. CONCLUSION: RRT incidence continues to rise but at various rates in the European countries studied, tending to widen the gap between them. This mainly results from enlarging differences in incidence in the elderly and, to a lesser extent, in that due to diabetes, hypertension and renal vascular disease.     

Recovery of renal function after 90 d on dialysis: implications for transplantation in patients with potentially reversible causes of renal failure

Abstract: Background: Late recovery of renal function in patients requiring dialysis is a well recognized but uncommon phenomenon. Moves to increase the number of live donor transplants and the recognition that early transplantation is associated with better graft survival means it is possible that patients who are going to recover renal function may be transplanted unnecessarily. Design: Prospective survey of patients receiving dialysis for more than 90 d in south west Scotland from 1 January 1994 to 31 December 2005. Methods: Routine measurement of residual renal function by combined urea and creatinine clearance allowed us to detect late recovery whenever this occurred. Results: Eight of 202 (4%) patients recovered sufficient renal function to stop dialysing after 90‐d treatment. The likely cause of the renal failure in five of these patients was atheroembolism. One with atherosclerotic renovascular disease had been stented and would have received a live related renal transplant had his sister not had second thoughts about the procedure. Conclusion: It may be sensible to postpone transplantation in patients with certain types of renal failure, perhaps particularly patients with renovascular disease who have recently undergone a failed revascularization procedure.     

Cigarette smoking accelerates progression of renal failure in primary renal disease. A prospective study in parallel group design with matched groups

There is substantial evidence for the adverse impact of smoking on deterioration of renal function in diabetic nephropathy but very little information is available concerning effects of smoking on the evolution of other renal diseases. In a prospective study in parallel group design with matched groups, 45 cigarette smoking patients (≥ 1 pack/day) with glomerular or tubulointerstitial lesions were compared with 45 non‐smoking patients matched for age, gender, cause and severity of renal disease as well as presence of hypertension. The monthly decline of creatinine clearance was significantly faster in smoking patients than in non‐smoking patients (follow‐up period 2 years) (1.25 mL/min vs 0.67 mL/min, P < 0.001). Smoking promoted progression of both glomerular and tubulointerstitial nephropathy. This effect occurred independently of changes in blood pressure, proteinuria or lipid concentration. The results of this investigation indicate that cigarette smoking is an independent risk factor not only for diabetic but also for non‐diabetic nephropathies.     

Patterns of renal disease in South Africa

Summary: The prevalence and patterns of renal disease in the different racial groups in South Africa is reviewed. South Africa is populated by four groups: Blacks, Whites, Indians and 'Coloured' or Mixed race. In 1994, the South African Dialysis and Transplant Registry (SADTR) recorded 3399 patients (99 pmp) on treatment for end-stage renal failure (ESRF). Glomerulonephritis (GN) was recorded as the cause of ESRF in 1771 (52.1%) patients and hypertension (HPT) in 1549 (45.6%) patients. In a study of 394 patients with ESRF in our unit, HPT was the cause of ESRF in 32% of Blacks and 24% of Indians, GN in 25% of Blacks and Indians and 33% of 'Coloured' patients, while analgesic nephropathy caused ESRF in 33% of White patients. A study of 3632 patients with ESRF reported HPT as the aetiology in 4.3% of Whites, 13.8% of Indians and 34.6% of Blacks, with 57% of the latter having malignant hypertension. of adult Black patients with primary GN, 36% had mesangiocapillary GN, while 21% had membranous GN and 10.7% minimal change disease. Black children have a low prevalence of minimal change disease: 13.5% compared with 75% in Indians. IgA nephropathy is rare in Blacks and has been reported in two patients in another study. Hepatitis B infection occurred in 73% of Black children with membranous GN. Prevalence data for hepatitis C-associated GN is lacking, but antibody-positive figures of 4.8–21% have been reported in South African dialysis and transplant patients. Prevalence figures for HIV-associated renal disease are not available. Public health measures are being actively implemented and should modify the prevalence and pattern of renal disease in South Africa.     

Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis

Aim:   Patients with end-stage renal disease (ESRD) often start long-term haemodialysis (HD) thrice weekly, regardless of the level of residual renal function (RRF). In this study, we investigated whether ESRD patients having sufficient RRF can be maintained on twice-weekly HD, and how they fare compared to patients without RRF on thrice-weekly HD.
Methods:   We analyzed 74 patients who had undergone long-term HD and maintained on the same dialysis frequency from February 1998 to July 2005, and followed until December 2005. We compared the clinical variables between twice-weekly and thrice-weekly HD patients and a second analysis testing the residual urine output as an independent predictor for twice-weekly HD.
Results:   After a mean follow up of 18 months, twice-weekly HD patients ( n  = 23) had lower serum β2-microglobulin than thrice-weekly HD patients ( n  = 51). Moreover, the twice-weekly group had a slower decline of RRF, as indicated by their higher urine output and creatinine clearance, fewer intradialytic hypotensive episodes, and required less frequent hospitalization. There was no difference between the two groups in cardiothoracic ratio or indices of nutrition and inflammation. Multivariable logistic regression identified age (odds ratio (OR), 1.866; 95% CI, 1.093–3.183), dry body mass index (OR, 0.790; 95% CI, 0.625–0.999), and urine output (OR, 1.093; 95% CI, 1.026–1.164) as predictors for maintaining twice-weekly HD.
Conclusion:   Our data suggest that when patients who have sufficient urine output are given twice-weekly HD, they maintain dialysis adequacy and exhibit better preservation of RRF than patients on thrice-weekly HD.     

Renal transplantation in indigenous populations

Summary: Renal disease is a common problem in many indigenous populations, but the treatment of endstage renal disease (ESRD) by dialysis and transplantation presents special problems in such populations. Many of these problems are illustrated by the attempts to provide renal transplantation for the Aboriginal Australian population. Factors such as cost, religious and cultural attitudes, endemic infections, causes of end-stage renal failure, compliance, race, logistic problems and equitable allocation of organs influence not only the provision of transplantation but also its outcome. In developing countries where cost is the overriding factor determining provision, transplantation even in the non-indigenous populations is rarely a practical option for ESRD. In developed and affluent countries, such as Australia, cost is not the major factor to be considered in providing a satisfactory renal transplant program. Cultural attitudes, compliance, logistic problems, and the equitable allocation of organs are greater problems. Nevertheless in developed countries such as Australia it should be possible to provide successful renal transplantation for the indigenous population with ESRD provided that it is accompanied by intense programs of disease prevention, after identification of the causes and risk factors of renal disease. Furthermore, a successful program will only be developed if it involves the indigenous communities themselves in the development and maintenance of the program.     

The impact of severe acute kidney injury requiring renal replacement therapy on survival and renal function of heart transplant recipients – a UK cohort study

Severe acute kidney injury (AKI), defined as requiring renal replacement therapy (RRT), is associated with higher mortality postheart transplantation, but its long-term renal consequences are not known. Anonymized data of 3365 patients, who underwent heart transplantation between 1995 and 2017, were retrieved from the UK Transplant Registry. Multivariable binary logistic regression was performed to identify risk factors for severe AKI requiring RRT, Kaplan–Meier analysis to compare survival and renal function deterioration of the RRT and non-RRT groups, and multivariable Cox regression model to identify predicting factors of mortality and end-stage renal disease (ESRD). 26.0% of heart recipients received RRT post-transplant. The RRT group has lower survival rates at all time points, especially in the immediate post-transplant period. However, conditional on 3 months survival, older age, diabetes and coronary heart disease, but not post-transplant RRT, were the risk factors for long-term survival. The predicting factors for ESRD were insulin-dependent diabetes, renal function at transplantation, eGFR decline in the first 3 months post-transplant, post-transplant severe AKI and transplantation era. Severe AKI requiring RRT post-transplant is associated with worse short-term survival, but has no impact on long-term mortality. It also accelerates recipients’ renal function deterioration in the long term.     

An unusual case of renovascular hypertension-renal artery stenosis of a pelvic kidney with aberrant blood supply.

Case Mr. G.L. aged 32 was referred to the Department of Renal Medicineat Derby City Hospital with unexplained hypertension. At 13years of age he had suffered a cerebrovascular accident causinga left hemiparesis. At the time there were no risk factors identifiedto account for his stroke including normal intracerebral arteries.During his