Population-based screening for family history of end-stage renal disease among incident dialysis patients

BACKGROUND: We determined the familial aggregation of end-stage renal disease (ESRD) in a large, population-based sample of incident ESRD cases to assess the feasibility of developing a targeted screening and prevention program directed at members of families at high risk for kidney disease. METHODS: Between January 1, 1995, and December 31, 2003, incident dialysis patients in ESRD Network 6 facilities were asked to complete a voluntary questionnaire on family history (FH) of ESRD. Cases with ESRD attributed to Mendelian diseases or urologic causes were excluded. FH was considered present if first- or second-degree relatives had ESRD. De-identified FH data were collated with demographic data at dialysis initiation. RESULTS: More than 46% of eligible patients (25,883/55,929) provided FH information and 22.8% (5,901/25,883) of these reported having a FH of ESRD. FH of ESRD was positively associated with female gender, earlier age at ESRD onset, and primary cause of ESRD, and negatively associated with white race. FH associations with age, race, gender, and primary cause of renal failure remained statistically significant after simultaneous adjustment in a multivariate logistic regression model. CONCLUSIONS: Approximately 23% of incident dialysis patients have close relatives with ESRD. Far more are likely to have relatives with clinically silent proteinuria or chronic kidney disease (CKD), both risk factors for future cardiovascular events and ESRD. Physicians caring for patients with CKD should be aware of the marked familial aggregation of ESRD and consider focusing screening efforts on high-risk family members in an attempt to slow the exponential growth rate of kidney disease.     

End-stage renal disease after kidney donation: a single-center experience

PURPOSE: Although the risk of kidney donation has been determined in many studies to be low with respect to morbidity and mortality, it is important to keep in mind that patients are put at some risk when they donate an organ for transplantation. The reported incidence of end-stage renal disease (ESRD) among kidney donors ranges from 0.2% to 0.5% with varying follow-up times. Herein, we have reported four living kidney donors at our institution who progressed to ESRD. MATERIALS AND METHODS: We reviewed registry data and medical records of patients who underwent donor nephrectomy at our institution between October 1, 1959, and June 30, 2005, particularly cases who developed ESRD. RESULTS: Between October, 1959, and the end of June, 2005, 3591 kidney transplants were performed at our center including 1195 of the organs (33%) from living donors, whose mean age was 41.9 years. Four kidney donors (0.33%) developed ESRD. Their mean age at donation was 31 years; the mean age at ESRD development was 46.5 years. All four patients donated to siblings with renal failure. Two of the four (50%) had another first-degree relative who subsequently developed renal failure. Two of the four (50%) smoked tobacco subsequent to donor surgery, and one (25%) was obese. CONCLUSIONS: Progression to ESRD is rare among living renal donors. Kidney donation is safe when strict eligibility criteria are met. There may be an increased risk for progression to ESRD among donors with a family history of renal disease.     

Familiality of cardiovascular mortality in end-stage renal disease patients

A very high rate of cardiovascular (CV) death is well recognized in individuals with end-stage renal disease (ESRD). Besides many other factors, this excess risk may also be related to familiality. We tested this hypothesis by estimating the risk of CV death among both ESRD patients and their relatives. In this case-control study, we used the Utah Population Database (UPDB), which includes genealogy records, state-wide death certificates as well as other data sets. These have been linked to the University of Utah Health Sciences Enterprise Data Warehouse which provides multiple diagnosis data sources. Patients with ESRD either on dialysis or who received a kidney transplant were identified in the clinical databases at the University of Utah Dialysis Program and Kidney Transplant Program or from Utah death certificates. CV deaths were identified by the reporting on the death certificates. The relative risks for CV death, adjusted for several potential confounders in the ESRD patients (n = 516) and in their first-degree (n = 2,418) and second-degree (n = 7,720) relatives were estimated in relation to the general population. Using information from death certificates, ESRD patients were found to have disproportionately increased risk for CV mortality (relative risk or RR = 2.4; 95% CI 2.11-2.72), compared to the general population. First-degree relatives of ESRD patients were also found to have an increased CV mortality risk (RR = 1.10; 95% CI 1.01-1.20). When the specific categories of CVD were analyzed, the first-degree relatives also had higher risks for death from acute myocardial infarction (RR = 1.20; 95% CI 1.03-1.40) or heart failure (RR = 1.32; 95% CI 1.12-1.56). An increased risk for CV mortality was, however, not observed in second-degree relatives of ESRD patients, except for the subcategory of hypertensive heart disease (RR = 1.24, 95% CI 1.01-1.49). In conclusion, this study suggests that, in addition to many putative risk factors, the increased risk of CV death in ESRD patients may have a familial contribution.     

Family history of end-stage renal disease among hemodialyzed patients in Poland

BACKGROUND: In previous reports of end-stage renal disease (ESRD) patients, family history of ESRD was associated with race, younger age, higher education levels and ESRD etiology. This study aimed to analyze how often Polish caucasian dialysis patients reported relatives with ESRD, and to evaluate which risk factors are associated with family history of ESRD. METHODS: 4808 ESRD patients provided data about renal disease etiology, diabetes and hypertensive status of first- and second-degree relatives, socioeconomic status and education level. RESULTS: Reported ESRD etiologies were: chronic glomerular disease, 19.4 %; diabetic nephropathy, 11.3%; interstitial nephritris, 11.2%; hypertension, 7.8%; polycystic kidney disease (PKD), 7.1%; other or no response, 40.0%. Positive ESRD family history was reported by 745 patients (15.5%); positive history of diabetes, 932 (19.4%); hypertension, 1904 (39%). Positive ESRD family history according to kidney disease etiology was: PKD, 53.1%; glomerulonephritis, 12%; diabetic nephropathy, 11.9%; hypertension, 11.8%; interstitial nephritis, 10.8%. PKD as ESRD etiology (odds ratio (OR) 8.06, 95% confidence interval (CI) 6.35-10.23, p < 0.0001), positive family history of diabetes (OR 1.64, 95% CI 1.34-1.99, p < 0.0001) and positive history of hypertension (OR 1.64, 95% CI 1.39-1.95, p < 0.0001), were independently associated with positive ESRD history. Patients with later ESRD onset had a less frequent positive ESRD family history: for ESRD < 45 yrs, 16% (OR 1.0); 45-64 yrs, 14.4% (OR 0.83, 95% CI 0.70-0.99); > or = 65 yrs, 9.2 % (OR 0.5, 95% CI 0.35-0.72). CONCLUSIONS: Results of our study strongly support the contention that familial predisposition contributes to ESRD development.     

Association between attributed cause of end-stage renal disease and risk of death in Brazilian patients receiving renal replacement therapy

BACKGROUND: Studies conducted in several countries have indicated that the survival of patients undergoing renal replacement therapy (RRT) depends on the attributed cause of end-stage renal disease (ESRD). OBJECTIVES: This study was conducted to evaluate the association between attributed cause of ESRD and mortality risk in RRT patients in Brazil. METHODS: We analyzed 88,881 patients from the Brazilian Ministry of Health Registry who were undergoing RRT between April 1997 and July 2000. Cox proportional hazards models were used to estimate the relative risk (RR) of death in patients with ESRD secondary to diabetes mellitus (DM), polycystic kidney disease (PKD), and primary glomerulopathies (GN) compared with a reference group comprised of patients with ESRD caused by hypertensive nephropathy. Patient's age, gender, and length of time (years) in RRT before inclusion in the registry (vintage) were included in the adjusted Cox model. RESULTS: Compared with the reference group, the mortality risk was 27% lower in patients with PKD (RR=0.73, 95% CI: 0.65-0.83, p<0.0001); 29% lower in patients with GN (RR=0.71, 95% CI: 0.68-0.74, p<0.0001); and 100% greater in DM patients (RR=2.00, 95% CI: 1.92-2.10, p<0.0001). These relative risks remained statistically significant after adjustment for age, gender, and length of time in RRT before inclusion in the registry. CONCLUSIONS: Our data indicate that compared with the patients with hypertensive nephrosclerosis as attributed cause of ESRD, patients undergoing RRT in Brazil with idiopathic glomerulopathy and polycystic kidney disease have a lower risk of mortality, and patients with diabetes mellitus have a greater risk of mortality.     

Transmission of G-protein beta3 subunit C825T alleles to offspring affected with end-stage renal disease.

BACKGROUND: Results of epidemiological studies have suggested that a hereditary predisposition to the development of chronic renal failure exists, and that such predisposition might be independent from underlying etiology of kidney disease. On the other hand, high blood pressure contributes substantially to a faster rate of progression of renal damage, regardless of underlying etiology of kidney disease. In this study we tested whether GNB3 C825T polymorphism, previously reported to be associated with hypertension, contributes to predisposition to end-stage renal disease (ESRD). METHODS: GNB3 polymorphism was genotyped in 247 family trios: offspring affected with ESRD and both parents, and transmission/disequilibrium test was used to establish the allele-phenotype association. Among the examined offspring, 47 patients had ESRD in the course of type 1 diabetes and diabetic nephropathy, 120 had primary glomerulonephritis and 80 had interstitial nephritis. We observed no significant differences between the GNB3 C and T allele transmission from heterozygous parents to affected offspring. RESULTS: In the overall group of examined patients, the C:T allele transmission (%) was 48:52, while in patients with diabetic nephropathy, chronic glomerulonephritis and chronic interstitial nephritis the transmission was (%) 50:50, 48:52 and 48:52, respectively. CONCLUSION: The results of our study suggest that GNB3 C825T polymorphism does not contribute substantially to the increased risk of the development of ESRD.     

A population-based assessment of the familial component of chronic kidney disease mortality

BACKGROUND/AIM: While the familial nature of chronic kidney disease (CKD) has been recognized, it has primarily been defined from studies of first-degree relatives of selected sets of cases. The goal of this study is an evaluation of the familial clustering of end-stage renal disease (ESRD) and CKD mortality using a population-based genealogy of Utah. This is the first population-based analysis of the familial component of ESRD and non-ESRD CKD. METHODS: We have defined two distinct patient groups for this analysis, using individuals with death certificates in the Utah Population Database indicating ESRD (n = 192) and non-ESRD CKD (n = 335) as the cause of death. Two measures of familiality were used: (1) relative risk (RR) of CKD or ESRD death in relatives of cases and (2) an average relatedness statistic, i.e., the Genealogical Index of Familiality. RESULTS: The RR for dying with ESRD among the first-degree relatives of individuals dying with ESRD is estimated to be 10.1 (p = 0.0007, 95% confidence interval CI 2.76-25.95), but is not significantly elevated among second-degree relatives. The RR for dying with non-ESRD CKD among first- and second-degree relatives of individuals dying with non-ESRD CKD was 3.89 (p = 0.0051, 95% CI 1.43-8.46) and 3.11 (p = 0.04, 95% CI 0.85-7.95), respectively. The Genealogical Index of Familiality statistic demonstrated that the individuals dying with ESRD are significantly more related than expected in this population (p = 0.013); significant excess relatedness was also observed for individuals dying with non-ESRD CKD (p = 0.006), suggesting a familial component for both, with evidence for common environmental and genetic effects. CONCLUSION: The results of this analysis of individuals dying with ESRD and non-ESRD CKD supports a significant and independent familial component to both conditions, suggesting a heritable factor playing a role.     

Anticipation of end stage renal disease in patients with autosomal dominant polycystic kidney disease in successive generations.

Autosomal dominant polycystic kidney disease is a disorder, which is inherited in 50% of offspring, irrelevant the sex and it has a variable clinical expressivity. Initially it was noticed that the clinical expression was interfamilial, but some studies found out that it was different. The aim of this study was to evaluate the age of onset of end-stage renal disease (ESRD) in affected parents in comparison with their offspring in successive generations. We studied 60 families of patients with autosomal dominant polycystic kidney disease (ADPKD). The diagnosis was done by echo criteria and we included only the patients for whom we knew precisely the onset of ESRD (affected parent and offspring), the sex of the parent who suffered from the disease, and offspring. We found out that the ESRD in ADPKD appears at the same age in affected parents and offspring (49,3 +/- 7,9 Vs 51,8 +/- 9,2, p = NS) irrelevant of the sex of the offspring. Patients with paternal inheritance (n = 38) were diagnosed to have ESRD earlier than their affected parents (47,9 +/- 8,3 Vs 52,2 +/- 9,2 p < 0,05), but patients with maternal inheritance had no difference (n = 22) (51,9 +/- 6,8 Vs 51,2 +/- 9,4, p = NS). In all the patients (60 couples) the survival rate was the same between affected parents and offspring (p = NS, Kaplan-Meier test), but significant differences were noticed between offspring with paternal inheritance in comparison with their parents (p < 0,05). In conclusion, we have detected that the onset of ESRD between patients with ADPKD in successive generations: a) Occurs in offspring as in their ancestors, b) anticipation was observed in 55% of couples, c) the sex of offspring does not have any relation with the renal death and d) the ESRD in patients with paternal inheritance occurs earlier in offspring than in their ancestors but not with maternal.     

Chronic renal failure in Al-Anbar of Iraq

There is no precise study of the epidemiology and prevalence of chronic renal failure in Al-Anbar, Iraq. Therefore, we studied 230 hemodialysis (HD) patients at the HD unit of Al-Ramadi teaching hospital during the period from April 1, 2008 to April 1, 2009. There were 124 (53%) male patients with a mean age of 48 ± 18.5 years, and 146 (63%) patients were older than 40 years. The estimated prevalence of chronic renal failure was 141 patients per million population. Diabetes mellitus (33%) and hypertension (22.6%) were the most common causes of chronic renal failure, followed in order by obstructive uropathy in 17.3%, undetermined causes in 14%, pyelonephritis in 4.7%, glomerulonephritis in 4.3%, and polycystic kidney disease in 3.9%. This study suggests that large number of patients with end-stage renal disease (ESRD) have diabetes and hypertension. However, those patients with undetermined cause still form a significant portion of etiology of ESRD, and this reflects late referral combined with diagnostic limitations.     

Transplantation in Diabetic Kidney Failure Patients: Modalities,Outcomes, and Clinical Management

Diabetes mellitus (DM) is a common and devastating disease, affecting up to 19.3 million Americans. It is the leading cause of chronic kidney disease (CKD) and end‐stage renal disease (ESRD) in the United States. Diabetic patients with ESRD have a high incidence of cardiovascular disease and death. For those kidney transplant patients with no history of DM prior to transplantation, the development of new onset diabetes after transplantation (NODAT) also poses a serious threat to both graft and patient survival. Kidney transplantation is the best renal replacement option for diabetic ESRD and has the potential to halt the progression of cardiovascular diseases. Early referral for transplant evaluation is essential for pre‐emptive or early kidney transplantation in this cohort of patients. In type 1 DM patients with ESRD, simultaneous pancreas and kidney transplantation (SPK) should be encouraged; and in patients facing prolonged waiting time for SPK transplantation but with an available living donor, living donor kidney transplantation followed by pancreas after kidney transplantation (PAK) is a suitable alternative. Islet transplantation in type 1 diabetics is deemed experimental by Medicare, and easy access to this modality remains restricted to qualified patients enrolled in clinical trials or with private insurance. The optimal management of kidney transplant patients with pre‐existent DM or NODAT involves a multi‐pronged approach consisting of pharmacological and nonpharmacological intervention to address all potential cardiovascular risk factors such as glycemic and lipid control, blood pressure control, weight loss, and smoking cessation. Finally, re‐transplantation should be recommended in suitable kidney transplant patients when the kidney allograft demonstrates continuous and progressive decline in function.     

Cardiovascular care in end-stage renal disease

Cardiovascular disease (CVD) accounts for the majority of morbidity and mortality in patients with end-stage renal disease (ESRD). Chronic kidney disease, and ESRD as its most severe form, are now acknowledged to be independent risk factors for CVD. The spectrum of CVD includes accelerated atherosclerosis, myocardial disease and heart failure, cardiac arrhythmias, and valvular heart disease. In addition, CKD and ESRD are independent and powerful factors that complicate cardiovascular procedures and have been directly linked to increased mortality. This issue of Advances in Chronic Kidney Disease will explore the spectrum of risk and the opportunities to improve care in ESRD in outpatient management, during dialysis, after kidney transplantation, and in coronary revascularization.     

Growth failure,risk of hospitalization and death for children with end-stage renal disease

Growth failure remains a significant problem for children with chronic renal insufficiency and end-stage renal disease (ESRD). We examined whether growth failure is associated with more-frequent hospitalizations or higher mortality in children with kidney disease. We studied data on prevalent United States pediatric patients with ESRD in 1990 who were followed through 1995. Patients were categorized according to the standard deviation score (SDS) of their incremental growth during 1990: severe (<–3 SDS), moderate growth failure (>–3 and <–2 SDS), and normal growth (>–2 SDS). Among 1,112 prevalent pediatric dialysis and transplant patients (<17 years, Tanner I–IV), those with severe and moderate growth failure had higher hospitalization rates {relative risk (RR) 1.14 [95% confidence interval (CI) 1.1, 1.2] and 1.24 [95% CI 1.2, 1.3]} respectively than those with normal growth after adjustment for age, gender, race, cause and duration of ESRD, and treatment modality (dialysis or transplant) in 1990. Kaplan-Meier survival analysis showed 5-year survival of 85% and 90% for patients with severe and moderate growth failure, respectively, compared with 96% for patients with normal growth (P<0.001, log-rank). Cox proportional hazards analysis revealed that those with severe (RR 2.9, 95% CI 1.6, 5.3) and moderate growth failure (RR 2.01, 95% CI 1.1, 3.6) had an increased risk of death compared with youths with normal growth, after adjustment. A higher proportion of deaths in the severe and moderate growth failure groups were attributed to infectious causes (22% and 18.7%, respectively) than in the normal growth group (15.6%). We conclude that growth failure is associated with a more-complicated clinical course and increased risk of death for children with kidney failure. Received: 15 August 2001 / Revised: 14 January 2002 / Accepted: 15 January 2002     

Factors influencing the development of end-stage renal disease

Epidemiological evidence is needed to design effective strategies for preventing chronic kidney disease (CKD) and end-stage renal disease (ESRD). Several types of health check are routinely performed in Japan, including the screening of asymptomatic individuals, but the potential benefits of these procedures remain unknown. We evaluated the predictors of ESRD, using community-based mass screening and a dialysis registry. This approach revealed the significance of proteinuria, hypertension, obesity, anemia, and high fasting plasma glucose levels (which indicate diabetes mellitus; DM), for the risk of developing ESRD. Lifestyle-related factors, such as smoking, alcohol consumption, and low levels of exercise, are also associated with these conditions and, in particular, with a high risk of ESRD. Over-nutrition and low levels of exercise can ultimately lead to DM, hypertension, hyperlipidemia, and obesity, and are important risk factors worldwide for cardiovascular diseases, CKD, and ESRD. The early detection and treatment of predictors of ESRD, along with appropriate treatment for CKD, may decrease the incidence of ESRD. In addition, the economic burden caused by the costs of dialysis presents a compelling argument for implementing a cost-effective preventive strategy against ESRD.     

Dyslipidaemia and the progression of renal disease in chronic renal failure patients.

BACKGROUND: Dyslipidaemia is common in patients with chronic renal failure (CRF), and there is increasing evidence to support the role of dyslipidaemia as a contributing factor in the progression of chronic renal disease. However, few prospective studies have been carried out which address the possible relationship between dyslipidaemia and the rate of progression of renal disease in patients with renal failure. METHODS: Between January 1985 and December 1997, we prospectively assessed the risk of CRF progression to dialysis in a cohort of 138 patients. Forty CRF patients reached end-stage renal disease (ESRD) and had to start supportive therapy during the follow-up period [group ESRD(+)]. The remaining 98 CRF patients served as controls [group ESRD(-)]. Potential clinical and laboratory risk factors for more rapid CRF decline to dialysis, including lipid abnormalities and baseline creatinine clearance were determined at the start of the follow-up period. RESULTS: Several significant differences were found in univariate analysis between the two groups of CRF, ESRD(+) and ESRD(-), namely a shorter follow-up period, a lower level of baseline creatinine clearance, a faster rate of creatinine clearance decline, a higher level of serum triglycerides, fibrinogen, total homocyst(e)ine and proteinuria, and a lower level of serum high-density lipoprotein in the ESRD(+) group than in the ESRD(-) group. However, by multivariate Cox analysis proteinuria [relative risk (95% confidence interval) 1.32 (1.16-1.50) for each g/day P = 0.001], baseline creatinine clearance [0.53 (0.40-0.70) for each 10 ml/min, P = 0.001] and chronic interstitial nephritis and hypertensive nephrosclerosis [0.38 (0.17-0.84) for presence, P = 0.005] were the only significant risk factors for CRF progression to dialysis. Hypertriglyceridaemia and male gender were selected in the final model, but were of borderline significance. CONCLUSIONS: These results suggest a limited role for dyslipidaemia in the progression of chronic renal disease to dialysis in CRF patients, in contrast with the powerful influence of proteinuria, baseline creatinine clearance and nephropathy type in predicting this progression.     

Predictors of diabetic end‐stage renal disease in Japan

SUMMARY: Diabetes mellitus (DM) has been the leading cause of incident dialysis in Japan since 1998, according to the Japanese Society for Dialysis Therapy (JSDT). In particular, the number of male DM dialysis patients is increasing. DM is becoming a worldwide epidemic in both developed and developing countries. Strategies to detect individuals at high‐risk of developing CKD and end‐stage renal disease (ESRD) are needed that can be implemented on a population‐basis. Among the commonly measured variables, dipstick urinalysis (proteinuria, haematuria), blood pressure, serum creatinine, body mass index (BMI), and serum uric acid are significant predictors of ESRD. Recently, we evaluated the effect of DM as a risk factor of developing ESRD. DM was diagnosed when the fasting plasma glucose (FPG) was 126 mg/dL or more in participants (n = 78529) of the 1993 screening program in Okinawa. The prevalence of DM was 5.2%. The odds ratio (95% CI) of DM for developing ESRD was 3.098 (1.738–5.525, P = 0.0001) after adjusting for possible confounding variables. Early detection and treatment of DM might prevent DM‐related ESRD. We examined 7125 non‐DM screenees who underwent a 1‐day health check between April 1997 and March 1998. They were followed‐up until March 2000 to determine whether they developed DM. Over the 2 years, the cumulative incidence of DM was 2.3%, 2.9% in men and 1.3% in women. Proteinuria was the most robust predictor of the development of DM; the adjusted relative risk (95% CI) was 1.90 (1.14–3.17). Obesity, per se, is also recognized as a risk factor for developing proteinuria. The higher the BMI, the higher the risk of developing ESRD; the adjusted odds ratio (95% CI) was 1.273 (1.121–1.446, P = 0.0002) for men. Other than being overweight (BMI = 25.0 kg/m²), a smoking habit was a significant predictor of developing proteinuria. The prevalence of obesity and DM is increasing in Japan. It is possible that the impact of obesity and complications of DM are different among races and ethnicities. Public relations regarding the risk of DM and its complications are especially important in Asian countries. Asians have more fat than non‐Asians, even at the same BMI levels. Knowledge of the predictors of DM‐ESRD is crucial as a first step toward prevention. Consistent with this notion, initiatives on the management of CKD and ESRD were recently organized in Japan and internationally.     

Development and internal validation of machine learning algorithms for end-stage renal disease risk prediction model of people with type 2 diabetes mellitus and diabetic kidney disease

AimsDiabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and is associated with increased morbidity and mortality in patients with diabetes. Identification of risk factors involved in the progression of DKD to ESRD is expected to result in early detection and appropriate intervention and improve prognosis. Therefore, this study aimed to establish a risk prediction model for ESRD resulting from DKD in patients with type 2 diabetes mellitus (T2DM).MethodsBetween January 2008 and July 2019, a total of 390 Chinese patients with T2DM and DKD confirmed by percutaneous renal biopsy were enrolled and followed up for at least 1 year. Four machine learning algorithms (gradient boosting machine, support vector machine, logistic regression, and random forest (RF)) were used to identify the critical clinical and pathological features and to build a risk prediction model for ESRD.ResultsThere were 158 renal outcome events (ESRD) (40.51%) during the 3-year median follow up. The RF algorithm showed the best performance at predicting progression to ESRD, showing the highest AUC (0.90) and ACC (82.65%). The RF algorithm identified five major factors: Cystatin-C, serum albumin (sAlb), hemoglobin (Hb), 24-hour urine urinary total protein, and estimated glomerular filtration rate. A nomogram according to the aforementioned five predictive factors was constructed to predict the incidence of ESRD.ConclusionMachine learning algorithms can efficiently predict the incident ESRD in DKD participants. Compared with the previous models, the importance of sAlb and Hb were highlighted in the current model.

Highlights

• What is already known? Identification of risk factors for the progression of DKD to ESRD is expected to improve the prognosis by early detection and appropriate intervention.
• What this study has found? Machine learning algorithms were used to construct a risk prediction model of ESRD in patients with T2DM and DKD. The major predictive factors were found to be CysC, sAlb, Hb, eGFR, and UTP.
• What are the implications of the study? In contrast with the treatment of participants with early-phase T2DM with or without mild kidney damage, major emphasis should be placed on indicators of kidney function, nutrition, anemia, and proteinuria for participants with T2DM and advanced DKD to delay ESRD, rather than age, sex, and control of hypertension and glycemia.

     

Familial clustering of chronic kidney disease

The incidence and prevalence rates of most forms of chronic kidney disease (CKD) had steadily been increasing for the past 30 years, although these rates now appear to have reached a plateau. It is clear that an individual's likelihood of developing progressive CKD results from complex interactions between multiple genetic and environmental factors. Familial clustering of CKD and end-stage renal disease (ESRD) is observed among all the common etiologies of nephropathy. This article reviews the epidemiology of the familial clustering of kidney disease, as well as potential environmental and genetic contributors. The related impact of familial clustering of cardiovascular disease (CVD) and the impact of CVD on the current epidemic of ESRD is also discussed. It is imperative that nephrologists and primary care physicians recognize that individuals who have relatives with advanced nephropathy are themselves at high risk for subsequent kidney disease, proteinuria, and atherosclerotic cardiovascular complications. Until kidney failure genes are identified, it is reasonable to use "family history" (FH) as a surrogate marker for risk of future nephropathy. The detection of kidney disease genes holds great promise for detecting novel pathways that initiate renal fibrosis and lead to progressive loss of renal function. These pathways are likely to offer new therapies that may slow or halt development of chronic kidney failure.     

Polycystic kidney disease at end-stage renal disease in the United States: patient characteristics and survival

BACKGROUND: The patient characteristics and mortality associated with autosomal dominant polycystic kidney disease have not been characterized for a national sample of end-stage renal disease (ESRD) patients. METHODS: 375,152 patients in the United States Renal Data System were initiated on ESRD therapy (including patients who eventually received renal transplants) between January 1, 1992 and June 30, 1997 and analyzed in an historical cohort study of polycystic kidney disease. RESULTS: Of the study population, 5,799 (1.5%) had polycystic kidney disease. In logistic regression, polycystic kidney disease was associated with Caucasian race (odds ratio 3.31, 95% CI, 3.09-3.54), women (1.10, 1.04-1.16), receipt of renal transplant (4.15, 3.87-4.45), peritoneal dialysis (vs. hemodialysis, 1.37, 1.27-1.49), younger age, and more recent year of first treatment for ESRD. Use of pre-dialysis EPO but not the level of serum hemoglobin at initiation of ESRD was significantly higher in patients with polycystic kidney disease. Patients with polycystic kidney disease had lower mortality compared to patients with other causes of ESRD, but patients with polycystic kidney disease had a higher adjusted risk of mortality associated with hemodialysis (vs. peritoneal dialysis) compared to patients with other causes of ESRD (hazard ratio 1.40, 1.13-1.75). CONCLUSIONS: Hematocrit at presentation to ESRD was not significantly different in patients with polycystic kidney disease compared with patients with other causes of ESRD. Peritoneal dialysis is a more frequent modality than hemodialysis in patients with polycystic kidney disease, and patients with polycystic kidney disease had an adjusted survival benefit associated with peritoneal dialysis, compared to patients with other causes of renal disease.     

Continuum of renoprotection with losartan at all stages of type 2 diabetic nephropathy: a post hoc analysis of the RENAAL trial results

Renin angiotensin system inhibitor therapy is seldom offered to individuals who have diabetes and advanced chronic kidney disease because of safety concerns. In this post hoc, secondary analysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial, angiotensin antagonism risk/benefit profile was assessed in 1513 individuals with type 2 diabetes and overt nephropathy. Incidence of ESRD, hospitalizations for heart failure, withdrawals for adverse events, and proteinuria during losartan or conventional treatment were compared within three tertiles of baseline serum creatinine concentration (highest, 2.1 to 3.6 mg/dl; middle, 1.6 to 2.0 mg/dl; lowest, 0.9 to 1.6 mg/dl). Losartan decreased the risk of ESRD by 24.6, 26.3, and 35.3% in highest, middle, and lowest tertiles, respectively. For every 100 patients with serum creatinine >2.0, 1.6 to 2.0, or <1.6 mg/dl, respectively, 4 yr of losartan therapy was estimated to save 18.9, 8.4, and 2.9 ESRD events and US$1,502,855, US$1,021,770, and US$528,591 costs for renal replacement therapy. Losartan also decreased the hospitalizations for heart failure by 50.2 and 45.1, in the highest and middle tertile, respectively. Withdrawals for adverse events other than heart failure were comparable between tertiles and treatment groups. Proteinuria decreased more on losartan than on placebo in all tertiles (highest, 24 versus -8%; middle, 16 versus -8%; lowest, 15 versus -10%). In proteinuric individuals with type 2 diabetes, losartan therapy reduced ESRD and hospitalizations for heart failure and was well tolerated at all levels of renal function. Angiotensin II antagonism is a suitable and well-tolerated treatment for individuals with type 2 diabetes even with GFR levels approaching renal replacement therapy.