Population-based identification and temporal trend of children with primary nephrotic syndrome: The Kaiser Permanente nephrotic syndrome study.

INTRODUCTION: Limited population-based data exist about children with primary nephrotic syndrome (NS). METHODS: We identified a cohort of children with primary NS receiving care in Kaiser Permanente Northern California, an integrated healthcare delivery system caring for >750,000 children. We identified all children <18 years between 1996 and 2012 who had nephrotic range proteinuria (urine ACR>3500 mg/g, urine PCR>3.5 mg/mg, 24-hour urine protein>3500 mg or urine dipstick>300 mg/dL) in laboratory databases or a diagnosis of NS in electronic health records. Nephrologists reviewed health records for clinical presentation and laboratory and biopsy results to confirm primary NS. RESULTS: Among 365 cases of confirmed NS, 179 had confirmed primary NS attributed to presumed minimal change disease (MCD) (72%), focal segmental glomerulosclerosis (FSGS) (23%) or membranous nephropathy (MN) (5%). The overall incidence of primary NS was 1.47 (95% Confidence Interval:1.27-1.70) per 100,000 person-years. Biopsy data were available in 40% of cases. Median age for patients with primary NS was 6.9 (interquartile range:3.7 to 12.9) years, 43% were female and 26% were white, 13% black, 17% Asian/Pacific Islander, and 32% Hispanic. CONCLUSION: This population-based identification of children with primary NS leveraging electronic health records can provide a unique approach and platform for describing the natural history of NS and identifying determinants of outcomes in children with primary NS.

Primary Nephrotic Syndrome and Risks of ESKD, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome Study.

BACKGROUND: Little population-based data exist about adults with primary nephrotic syndrome. METHODS: To evaluate kidney, cardiovascular, and mortality outcomes in adults with primary nephrotic syndrome, we identified adults within an integrated health care delivery system (Kaiser Permanente Northern California) with nephrotic-range proteinuria or diagnosed nephrotic syndrome between 1996 and 2012. Nephrologists reviewed medical records for clinical presentation, laboratory findings, and biopsy results to confirm primary nephrotic syndrome and assigned etiology. We identified a 1:100 time-matched cohort of adults without diabetes, diagnosed nephrotic syndrome, or proteinuria as controls to compare rates of ESKD, cardiovascular outcomes, and death through 2014, using multivariable Cox regression. RESULTS: We confirmed 907 patients with primary nephrotic syndrome (655 definite and 252 presumed patients with FSGS [40%], membranous nephropathy [40%], and minimal change disease [20%]). Mean age was 49 years; 43% were women. Adults with primary nephrotic syndrome had higher adjusted rates of ESKD (adjusted hazard ratio [aHR], 19.63; 95% confidence interval [95% CI], 12.76 to 30.20), acute coronary syndrome (aHR, 2.58; 95% CI, 1.89 to 3.52), heart failure (aHR, 3.01; 95% CI, 2.16 to 4.19), ischemic stroke (aHR, 1.80; 95% CI, 1.06 to 3.05), venous thromboembolism (aHR, 2.56; 95% CI, 1.35 to 4.85), and death (aHR, 1.34; 95% CI, 1.09 to 1.64) versus controls. Excess ESKD risk was significantly higher for FSGS and membranous nephropathy than for presumed minimal change disease. The three etiologies of primary nephrotic syndrome did not differ significantly in terms of cardiovascular outcomes and death. CONCLUSIONS: Adults with primary nephrotic syndrome experience higher adjusted rates of ESKD, cardiovascular outcomes, and death, with significant variation by underlying etiology in the risk for developing ESKD.

Contemporary rates and predictors of fast progression of chronic kidney disease in adults with and without diabetes mellitus.

BACKGROUND: Chronic kidney disease (CKD) is highly prevalent but identification of patients at high risk for fast CKD progression before reaching end-stage renal disease in the short-term has been challenging. Whether factors associated with fast progression vary by diabetes status is also not well understood. We examined a large community-based cohort of adults with CKD to identify predictors of fast progression during the first 2 years of follow-up in the presence or absence of diabetes mellitus. METHODS: Within a large integrated healthcare delivery system in northern California, we identified adults with estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73 m2 by CKD-EPI equation between 2008 and 2010 who had no previous dialysis or renal transplant, who had outpatient serum creatinine values spaced 10-14 months apart and who did not initiate renal replacement therapy, die or disenroll during the first 2 years of follow-up. Through 2012, we calculated the annual rate of change in eGFR and classified patients as fast progressors if they lost > 4 ml/min/1.73 m2 per year. We used multivariable logistic regression to identify patient characteristics that were independently associated with fast CKD progression stratified by diabetes status. RESULTS: We identified 36,195 eligible adults with eGFR 30-59 ml/min/1.73 m2 and mean age 73 years, 55% women, 11% black, 12% Asian/Pacific Islander and 36% with diabetes mellitus. During 24-month follow-up, fast progression of CKD occurred in 23.0% of patients with diabetes vs. 15.3% of patients without diabetes. Multivariable predictors of fast CKD progression that were similar by diabetes status included proteinuria, age ≥ 80 years, heart failure, anemia and higher systolic blood pressure. Age 70-79 years, prior ischemic stroke, current or former smoking and lower HDL cholesterol level were also predictive in patients without diabetes, while age 18-49 years was additionally predictive in those with diabetes. CONCLUSIONS: In a large, contemporary population of adults with eGFR 30-59 ml/min/1.73 m2, accelerated progression of kidney dysfunction within 2 years affected ~ 1 in 4 patients with diabetes and ~ 1 in 7 without diabetes. Regardless of diabetes status, the strongest independent predictors of fast CKD progression included proteinuria, elevated systolic blood pressure, heart failure and anemia.

Elevated BP after AKI.

The connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP--defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit--during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization.

Nonrecovery of kidney function and death after acute on chronic renal failure.

BACKGROUND AND OBJECTIVES: Relatively little is known about clinical outcomes, especially long-term outcomes, among patients who have chronic kidney disease (CKD) and experience superimposed acute renal failure (ARF; acute on chronic renal failure). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We tracked 39,805 members of an integrated health care delivery system in northern California who were hospitalized during 1996 through 2003 and had prehospitalization estimated GFR (eGFR) <45 ml/min per 1.73 m(2). Superimposed ARF was defined as having both a peak inpatient serum creatinine greater than the last outpatient serum creatinine by > or =50% and receipt of acute dialysis. RESULTS: Overall, 26% of CKD patients who suffered superimposed ARF died during the index hospitalization. There was a high risk for developing ESRD within 30 d of hospital discharge that varied with preadmission renal function, being 42% among hospital survivors with baseline eGFR 30-44 ml/min per 1.73 m(2) and 63% among hospital survivors with baseline eGFR 15-29 ml/min per 1.73 m(2). Compared with patients who had CKD and did not experience superimposed ARF, those who did had a 30% higher long-term risk for death or ESRD. CONCLUSIONS: In a large, community-based cohort of patients with CKD, an episode of superimposed dialysis-requiring ARF was associated with very high risk for nonrecovery of renal function. Dialysis-requiring ARF also seemed to be an independent risk factor for long-term risk for death or ESRD.