Favorable therapeutic efficacy of low-density lipoprotein apheresis for nephrotic syndrome with impaired renal function.

Many reports have shown the therapeutic efficacy of LDL apheresis (LDL-A) in drug-resistant nephrotic syndrome (NS) for improvement of heavy proteinuria and severely impaired renal function. To obtain comprehensive results in a large number of cases, a post hoc analysis of the Prospective Observational survey on the Long-Term Effects of the LDL-Apheresis on the Drug Resistant Nephrotic Syndrome (POLARIS) study was performed by stratifying enrolled cases according to the pretreatment estimated glomerular filtration rate (eGFR) levels indicating normal (N) (≥60 ml/min/1.73 m2 ), moderately impaired (M) (≥30 to <60 ml/min/1.73 m2 ), and severely impaired (S) (<30 ml/min/1.73 m2 ) renal function. Significant improvements of proteinuria and renal function were found in Group N and, most interestingly, in Group M. A tendency for improvement in proteinuria was found in Group S. Most cases in all groups had not entered end-stage renal disease at 2 years after LDL-A treatment. These results suggest that LDL-A has therapeutic efficacy even in cases in which renal function has declined to 30 ml/min/1.73 m2 .

Rationale and study design of a clinical trial to assess the effects of LDL apheresis on proteinuria in diabetic patients with severe proteinuria and dyslipidemia.

BACKGROUND: Diabetic nephropathy is a leading cause of end-stage kidney disease in the world. Although various types of treatment for diabetes, hypertension and dyslipidemia have improved prognosis and quality of life in patients with diabetic nephropathy, there still exist some diabetic patients with severe proteinuria showing poor prognosis. This clinical trial, LICENSE, aims to confirm the impact of LDL apheresis on proteinuria exhibiting hyporesponsiveness to treatment. METHODS: This ongoing trial is a multicenter, prospective study of diabetic patients with severe proteinuria. The objective is to examine the impact of LDL apheresis on proteinuria in patients with diabetic nephropathy. The other subject is to investigate safety of LDL apheresis in these patients. RESULTS: The subjects consist of diabetic patients with serum creatinine (Cr) levels below 2 mg/dL who present severe proteinuria above 3 g/g Cr or 3 g/day and LDL cholesterol above 120 mg/dL. The target number of registered patients will be 35 patients. Urinary protein excretion and renal function will be observed for 24 weeks after the treatment of LDL apheresis. CONCLUSION: This study will determine the effectiveness and safety of LDL apheresis for diabetic nephropathy patients with severe proteinuria and dyslipidemia.

Underestimating chronic kidney disease by urine dipstick without serum creatinine as a screening tool in the general Japanese population.

BACKGROUND: It is not known if urine dipstick alone can identify chronic kidney disease (CKD) in the general Japanese population. METHODS: We designed a cross-sectional study using data obtained in 2008 from a nationwide community-based health examination program for adults aged 40-74. The data consisted of blood tests, urine tests and questionnaire related to metabolic disorders. Those who had both serum creatinine measured and urine dipstick tested were analyzed. RESULTS: Data were obtained from 538,846 people with a mean age of 62.8 years, consisting of 41.6 % males. Our study showed that 14.4 % had an eGFR below 60 mL/min/1.73 m(2), 5.2 % had proteinuria and 18.1 % had CKD. Within the population with CKD, non-proteinuric CKD accounted for 71.4 %. The proportion of non-proteinuric CKD was highest in stage G3a (91.8 %) followed by G3b (77.0 %) disease, and was greater in the more elderly and in females. The proportion of non-proteinuric CKD was 47.9 % in diabetes mellitus, 69.3 % in dyslipidemia, 66.8 % in hypertension and 57.1 % in metabolic syndrome. Furthermore, non-proteinuric CKD accounted for 78.1 % of the population without these lifestyle diseases, suggesting that even in the population without apparent risk, CKD is still prevalent and can be missed when urine dipstick is the only screening method used. CONCLUSIONS: This study showed that a considerable population of CKD might be overlooked when only dipstick proteinuria is assessed for CKD screening. Hence, we strongly recommend that both urinalysis and serum creatinine measurement should be a part of the nationwide CKD screening system.

Risk factor profiles based on estimated glomerular filtration rate and dipstick proteinuria among participants of the Specific Health Check and Guidance System in Japan 2008.

BACKGROUND: Estimated glomerular filtration rate (eGFR) and albuminuria (proteinuria) are both important determinants of the risk of cardiovascular disease (CVD), end-stage renal disease (ESRD), and mortality. Few studies, however, have examined the risk factor profiles based on eGFR and proteinuria among the general population. METHODS: Data of the newly developed nationwide screening program of the Specific Health Check-up and Guidance System (Tokutei-Kensin) initiated in 2008 were used in this study. The aim of this screening, targeting people 40-74 years of age, was to detect those with metabolic syndrome and to offer those services regarding lifestyle modifications that will lead to the reduction of diabetes mellitus (DM) and DM-related ESRD. Individual records of 580,000 participants in 69 cities and towns and 3 union cohorts throughout Japan were anonymously provided and included in the present study. RESULTS: Details of 332,174 participants (57.3% of the total) with both serum creatinine and dipstick urine test data were analyzed. Mean (SD) age was 63.6 (8.3) years and 40.6% were men. The mean (SD) eGFR was 75.0 (16.2) ml/min/1.73 m(2) and 5.4% had proteinuria. The prevalence of chronic kidney disease (CKD) stage 3, 4, and 5 was 14.2%, 0.2%, and 0.07%, respectively. The prevalence of DM, hypertension, and history of stroke and heart disease was correlated with the combination of eGFR and degree of proteinuria. CONCLUSION: The findings of the present study indicate that CKD and risk factors for CVD are quite common among middle-aged Japanese. CKD classification based on eGFR and proteinuria may be useful for predicting CVD, mortality rate, and ESRD in the Japanese population.

Weight gain after 20 years of age is associated with prevalence of chronic kidney disease.

BACKGROUND: Weight gain after maturity is a risk factor for diabetes, coronary heart disease, and stroke, even in individuals with a normal body mass index; however, there is little information about the influence of weight gain after maturity on chronic kidney disease (CKD). Therefore, we examined the association between weight gain after 20 years of age and the prevalence of CKD. METHODS: A cross-sectional study was performed on 28,151 women and 21,110 men aged between 40 and 59 years who participated in the specific health check and guidance system of Japan in 2008. We compared prevalence of CKD between participants with and without weight gain of at least 10 kg after 20 years of age. Multivariate logistic regression models and stratified analyses were used to adjust for possible confounding factors. RESULTS: The prevalence of CKD among participants with weight gain was significantly higher than among those without weight gain both in women (11.8 vs 8.3%, p < 0.0001) and in men (12.2 vs 9.2%, p < 0.0001). After adjustment for age, smoking, regular exercise, alcohol intake, history of kidney disease, hypertension, diabetes, and hypercholesterolemia, the odds ratio (95% confidence interval) for CKD was 1.24 (1.14-1.36) in women and 1.15 (1.05-1.26) in men with weight gain of at least 10 kg after the age of 20 years. Even in participants without metabolic syndrome, weight gain was independently associated with CKD in both genders. CONCLUSIONS: Weight gain after 20 years of age is associated with CKD among Japanese, even those without metabolic syndrome.

Prevalence of chronic kidney disease in the Japanese general population.

BACKGROUND: We previously estimated the prevalence of chronic kidney disease (CKD) stages 3-5 at 19.1 million based on data from the Japanese annual health check program for 2000-2004 using the Modification of Diet in Renal Disease (MDRD) equation multiplied by the coefficient 0.881 for the Japanese population. However, this equation underestimates the GFR, particularly for glomerular filtration rates (GFRs) of over 60 ml/min/1.73 m(2). We did not classify the participants as CKD stages 1 and 2 because we did not obtain proteinuria data for all of the participants. We re-estimated the prevalence of CKD by measuring proteinuria using a dipstick test and by calculating the GFR using a new equation that estimates GFR based on data from the Japanese annual health check program in 2005. METHODS: Data were obtained for 574,024 (male 240,594, female 333,430) participants over 20 years old taken from the general adult population, who were from 11 different prefectures in Japan (Hokkaido, Yamagata, Fukushima, Tochigi, Ibaraki, Tokyo, Kanazawa, Osaka, Fukuoka, Miyazaki and Okinawa) and took part in the annual health check program in 2005. The glomerular filtration rate (GFR) of each participant was computed from the serum creatinine value using a new equation: GFR (ml/min/1.73 m(2)) = 194 x Age(-0.287) x S-Cr(-1.094) (if female x 0.739). The CKD population nationwide was calculated using census data from 2005. We also recalculated the prevalence of CKD in Japan assuming that the age composition of the population was same as that in the USA. RESULTS: The prevalence of CKD stages 1, 2, 3, and 4 + 5 were 0.6, 1.7, 10.4 and 0.2% in the study population, which resulted in predictions of 0.6, 1.7, 10.7 and 0.2 million patients, respectively, nationwide. The prevalence of low GFR was significantly higher in the hypertensive and proteinuric populations than it was in the populations without proteinuria or hypertension. The prevalence rate of CKD in Japan was similar to that in the USA when the Japanese general population was age adjusted to the US 2005 population estimate. CONCLUSION: About 13% of the Japanese adult population-approximately 13.3 million people-were predicted to have CKD in 2005.