Bariatric surgery is associated with improvement in kidney outcomes.

Severe obesity is associated with increased risk of kidney disease. Whether bariatric surgery reduces the risk of adverse kidney outcomes is uncertain. To resolve this we compared the risk of estimated glomerular filtration rate (eGFR) decline of ≥30% and doubling of serum creatinine or end-stage renal disease (ESRD) in 985 patients who underwent bariatric surgery with 985 patients who did not undergo such surgery. Patients were matched on demographics, baseline body mass index, eGFR, comorbidities, and previous nutrition clinic use. Mean age was 45 years, 97% were white, 80% were female, and 33% had baseline eGFR <90 ml/min per 1.73 m(2). Mean 1-year weight loss was 40.4 kg in the surgery group compared with 1.4 kg in the matched cohort. Over a median follow-up of 4.4 years, 85 surgery patients had an eGFR decline of ≥30% (22 had doubling of serum creatinine/ESRD). Over a median follow-up of 3.8 years, 177 patients in the matched cohort had an eGFR decline of ≥30% (50 had doubling of serum creatinine/ESRD). In adjusted analysis, bariatric surgery patients had a significant 58% lower risk for an eGFR decline of ≥30% (hazard ratio 0.42, 95% confidence interval 0.32-0.55) and 57% lower risk of doubling of serum creatinine or ESRD (hazard ratio 0.43, 95% confidence interval: 0.26-0.71) compared with the matched cohort. Results were generally consistent among subgroups of patients with and without eGFR <90 ml/min per 1.73 m(2), hypertension, and diabetes. Thus, bariatric surgery may be an option to prevent kidney function decline in severely obese individuals.

Estimated glomerular filtration rate variability and risk of end-stage renal disease among patients with Stage 3 chronic kidney disease.

BACKGROUND/AIMS: Dynamic changes in estimated glomerular filtration rate (eGFR) predict death among patients with chronic kidney disease (CKD). Whether variability in serial eGFR measurements is associated with risk of end stage renal disease (ESRD) has not been reported. METHODS: We retrospectively analyzed the risk of ESRD as a function of eGFR variability (defined as the absolute value of the difference between the obtained clinical eGFR value at a given time and the eGFR value estimated by the linear regression line at the same time point) among a cohort of patients with Stage 3 CKD. The study population was comprised of adult primary care patients enrolled at Geisinger Clinic between January 1, 2004 and December 31, 2006, with Stage 3 CKD and a minimum of 4 serum creatinine results during this 3-year window, and without history of solid-organ transplant or metastatic cancer. Cohort members were followed through March 31, 2011 for ESRD (identified through linkage with the USRDS dataset of ESRD, or first outpatient eGFR < 15 ml/min/1.73 m2). A multivariate Cox proportional hazard model (adjusted for demographic factors, co-morbid conditions, medications, hospital-associated acute kidney injury, proteinuria, kidney function, and serum albumin, among other factors) was developed to test the association of eGFR variability with ESRD. RESULTS: 4,219 patients met study criteria. Those with greater eGFR variability were more likely to have diabetes, cardiovascular disease, and better baseline kidney function than those with lesser variability. 193 (4.6%) of the overall cohort developed ESRD during a median follow-up of 3.8 years, while 596 (14.1%) died prior to study end without ESRD. Results of the multivariate-adjusted Cox proportional hazard model showed that eGFR variability is not associated with ESRD (HR 1.00 for the highest-variability quartile, relative to the lowest; 95% CI 0.66 - 1.51). CONCLUSION: eGFR variability does not predict ESRD among patients with Stage 3 CKD.

Readmission after hospitalization for heart failure among patients with chronic kidney disease: a prediction model.

AIMS: 30-day readmission rates after hospitalization for heart failure (HF) approach 25%, and patients with chronic kidney disease (CKD) are disproportionately represented. A retrospective cohort study was conducted to develop a prediction tool for 30-day readmission after hospitalization for HF among those with non-dialysis dependent CKD. METHODS: Geisinger primary care patients with Stage 3 - 5 CKD hospitalized with a primary discharge diagnosis of HF during the period July 1, 2004 through February 28, 2010 were eligible. Multivariate logistic regression was employed to build models from predictors of 30-day readmission, drawn from demographic, clinical, laboratory, and pharmaceutical variables in the electronic health record. Variables were manually removed to achieve a model with satisfactory goodness-of-fit and parsimony while maximizing area under the receiver operating characteristic curve (AUC). Internal validation was performed using the bootstrap resampling method (1,000 samples) to provide a bias-corrected AUC. RESULTS: 607 patients with CKD were admitted for HF during the study period; 116 (19.1%) were readmitted within 30 days. A model incorporating 23 variables across domains of medical history, active outpatient pharmaceuticals, vital signs, laboratory tests, and recent inpatient and outpatient resource utilization yielded an AUC (95% CI) of 0.792 (0.746 - 0.838). The bias-corrected AUC was 0.743. At an estimated readmission probability of 20%, the model correctly classified readmission status for 73% of the population, with a sensitivity of 69% and a specificity of 73%. CONCLUSION: A robust electronic health record may facilitate the identification of CKD patients at risk for readmission after hospitalization for HF.

Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury.

Acute kidney injury increases mortality risk among those with established chronic kidney disease. In this study we used a propensity score-matched cohort method to retrospectively evaluate the risks of death and de novo chronic kidney disease after reversible, hospital-associated acute kidney injury among patients with normal pre-hospitalization kidney function. Of 30,207 discharged patients alive at 90 days, 1610 with reversible acute kidney injury that resolved within the 90 days were successfully matched across multiple parameters with 3652 control patients who had not experienced acute kidney injury. Median follow-up was 3.3 and 3.4 years (injured and control groups, respectively). In Cox proportional hazard models, the risk of death associated with reversible acute kidney injury was significant (hazard ratio 1.50); however, adjustment for the development of chronic kidney injury during follow-up attenuated this risk (hazard ratio 1.18). Reversible acute kidney injury was associated with a significant risk of de novo chronic kidney disease (hazard ratio 1.91). Thus, a resolved episode of hospital-associated acute kidney injury has important implications for the longitudinal surveillance of patients without preexisting, clinically evident kidney disease.

Bisphosphonate therapy, death, and cardiovascular events among female patients with CKD: a retrospective cohort study.

BACKGROUND: Accelerated vascular calcification contributes to cardiovascular disease burden in patients with chronic kidney disease (CKD). We hypothesized that bisphosphonate therapy would reduce the risk of mortality and cardiovascular events in this population. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult women with stage 3 or 4 CKD receiving primary care in a large rural integrated health care system in 2004-2010. EXPOSURE: Time-dependent exposure status based on outpatient prescription for any medication within the bisphosphonate class, obtained from electronic health records. OUTCOMES: Time to death and first cardiovascular event (composite of myocardial infarction, heart failure, or stroke). RESULTS: Data from 9,604 eligible female patients with CKD were analyzed; 3,234 were treated with bisphosphonate therapy. During a median follow-up of 3.9 (25th-75th percentile, 2.3-5.4) years, there were 286 versus 881 deaths and 206 versus 571 cardiovascular events (treated vs not-treated groups, respectively). In a multivariate Cox proportional hazard model, the adjusted HR for death (treated vs not treated) was 0.78 (95% CI, 0.67-0.91; P = 0.003). In Cox modeling adjusted for similar baseline covariates, treatment with bisphosphonates was not associated with a lower risk of the composite cardiovascular outcome (adjusted HR, 1.14; 95% CI, 0.94-1.39; P = 0.2). LIMITATIONS: Residual confounding by unidentified factors, exclusion of male patients, and lack of information about longitudinal drug adherence. CONCLUSIONS: For female patients with CKD, treatment with bisphosphonates is associated with a lower risk of death, but not cardiovascular events. Confirmatory studies and investigations of potential causal mechanisms are warranted.

Need for payer-provider partnerships in addressing social determinants of health.

This article examines payer-provider partnerships in social determinants of health (SDoH) interventions, identifies important factors for an approach centered around return on investment (ROI) using integrated delivery and finance systems as case studies, and advocates for increased collaboration between payers and providers when addressing SDoH. Despite the numerous examples where payers and providers have attempted to independently address SDoH, there is limited evidence for the success of these interventions. Since most stakeholders individually do not have access to financial and clinical data, identifying an ROI for SDoH interventions is logistically challenging, but even when these data are available, stakeholders may not want to share their learnings due to negative findings and/or unwillingness to share proprietary information. These issues are further amplified by the effects of COVID-19 and its worsening effect on widening health disparities, but many payers and providers have risen to the challenge together. This article advocates for the importance of payer-provider partnerships to address SDoH and uses examples of integrated delivery and finance systems as case studies of how these partnerships could function. DISCLOSURES: No outside funding supported the writing of this article. Hartle is employed by Geisinger Health System. The other authors have nothing to disclose.

A prospective study of risk factors for nephrolithiasis after Roux-en-Y gastric bypass surgery.

PURPOSE: Roux-en-Y gastric bypass surgery has become an increasingly common form of weight management. Early retrospective reviews have suggested that new onset nephrolithiasis develops in some patients after undergoing Roux-en-Y gastric bypass. We present a prospective longitudinal study to assess risk factors for nephrolithiasis after Roux-en-Y gastric bypass. MATERIALS AND METHODS: A total of 45 morbidly obese patients scheduled to undergo Roux-en-Y gastric bypass surgery were enrolled in this prospective study between November 2006 and November 2007. Exclusion criteria included history of nephrolithiasis or inflammatory bowel disease. Serum uric acid, parathyroid hormone, calcium, albumin, and creatinine and 24-hour urine collections were obtained within 6 months before Roux-en-Y gastric bypass, and at 6 to 12 months postoperatively. A Wilcoxon signed-rank test was used to compare preoperative and postoperative serum laboratory values and 24-hour urine values. McNemar's test was used to determine if the percent of abnormal values underwent a statistically significant change after Roux-en-Y gastric bypass. For both statistical methods a p value was calculated for the change in each variable with p <0.05 considered statistically significant. RESULTS: Statistically significant changes included increased urinary oxalate and calcium oxalate supersaturation, and decreased urinary citrate and total urinary volume postoperatively. A statistically significant percentage of patients exhibited decreased urinary calcium, while a statistically significant percentage of patients experienced increased urinary oxalate and calcium oxalate supersaturation. CONCLUSIONS: Our prospective study demonstrated multiple factors that increase the relative risk of nephrolithiasis after Roux-en-Y gastric bypass. These changes may make stone formation after Roux-en-Y gastric bypass increasingly likely and pose an ongoing challenge in the realm of urology.

Outpatient erythropoietin administered through a protocol-driven, pharmacist-managed program may produce significant patient and economic benefits.

To assess the effect of a disease management program in anemia of chronic kidney disease (CKD), the authors reviewedthe records of all adults treated with epoetin alfa (EPO) at their institution between September 2003 and April 2006 and compared them with a group treated through a pharmacist-managed program with patients managed by PCPs in terms of time to target hemoglobin (Hb) (11-12.9 mg/dL), percent of Hb values maintained in target range, average weekly dose of EPO, and percent of iron-saturation (T-sat) values within target range (20%-50%) over a period of six months to one year. Although pharmacist-managed patients received lower weekly EPO doses than those managed by PCPs (6,698 vs. 12,000 units, respectively; P = .0001), they achieved goal Hb faster (47.5 vs. 62.5 days, P = .11) and maintained a higher percentage of Hb and T-sat values in target range (69.8% vs. 43.9%, P = .0001, and 64.8% (vs. 40.4%, respectively; P = .043). A pharmacist-managed program may present significant clinicaland economic benefits in anemia of CKD.

Campath-1H induction and the incidence of infectious complications in adult renal transplantation.

BACKGROUND: The purpose of this study was to evaluate adult renal transplantation patients who received a alemtuzumab (Campath-1H)-based induction protocol for the incidence of infectious complications. METHODS: We began using 30 mg Campath-1H intravenously for induction therapy in May 2003. The patients were treated with a maintenance regimen of tacrolimus or mycophenolate mofetil (MMF), and rapidly tapered prednisone; valganciclovir was used for CMV prophylaxis. Forty-nine adult patients who received renal transplants between May 1, 2003 and June 7, 2004 were included. The mean follow-up time was 13.7 months with a range of 10-24 months. Data were collected via a retrospective chart review. RESULTS: The infectious complications noted in the Campath-1H group were compared with a historical group of 56 patients receiving conventional immunosuppression. There was one case of cytomegalovirus (CMV) viremia and two cases of CMV disease (one pneumonitis and one enteritis). There were four cases of urinary tract infection and one extremity cellulitis. One patient developed Cryptococcal meningitis. Eight of the 49 (16%) patients in the Campath group had an infectious complication, compared to 18 out of 56 (32%) in the historical group. CONCLUSION: Campath-1H induction for renal transplantation appears to have a low incidence of associated infectious complications when compared to historical regimens.

Chronic active thrombotic microangiopathy in native and transplanted kidneys.

We report 2 complicated cases of thrombotic microangiopathy with chronic features and active components. The first case was a 36-yr-old woman with positive anti-DNA antibody and possible lupus cerebritis, who developed thrombotic microangiopathy secondary to a series of syndromes, including preeclampsia and anti-phospholipid antibody syndrome. Renal biopsy revealed no evidence of lupus nephritis and her renal function returned to normal 1 week after the biopsy. The second case was a 46-yr-old man who developed thrombotic microangiopathy of unknown etiology, which led to end-stage renal disease within 6 mo. The patient received a living related-donor transplant, but thrombotic microangiopathy recurred in the donor kidney only 40 days after the renal transplantation.

Case report: IgM type of membranous glomerulopathy in a diabetic patient.

We report the case of a 46-yr-old man with a 16-yr history of type I diabetes mellitus who developed rapid onset of nephrotic syndrome. Renal biopsy revealed diabetic nephropathy, characterized by thickened glomerular basement membranes (GBM), mild nodular glomerulosclerosis, and focal arteriolar hyalinization. Immunofluorescent (IF) studies showed strong granular IgM staining along glomerular loops, with subepithelial and intramembranous immune complex deposits along glomerular capillary loops demonstrated by electron microscopy (EM). These findings are consistent with membranous glomerulopathy with IgM as the predominant immunoglobulin. In addition, there were large aggregates of electron-dense material composed of numerous ring or spherical particles, ranging from 200 to 400 nm, in Bowman's space, which corresponded to eosinophilic aggregates on light microscopy (LM) and strong IgM stained materials by IF studies.

Monocyte-mediated acute renal rejection after combined treatment with preoperative Campath-1H (alemtuzumab) and postoperative immunosuppression.

Campath-1H (alemtuzumab), a humanized monoclonal antibody against CD52, can cause more profound depletion of lymphocytes than monocytes. The resultant imbalance of lymphocytes and monocytes after Campath-1H treatment of a renal-transplant recipient may lead to an acute rejection dominated by monocytes. We report such a case of acute transplant rejection in a 49-yr-old man who received a living non-related kidney transplant and was treated with preoperative Campath-1H and postoperative immunosuppression. An initial post-transplant renal biopsy showed diffuse mild acute rejection with 95% CD68-positive monocytes, but only 5% CD3-positive T lymphocytes. Inflammatory cells in the renal biopsy were negative for CD34 and CD1a stains, suggesting non-involvement of CD34-derived dendritic cells in the acute rejection. After steroid treatment for 2 wk, the patient's serum creatinine concentration diminished to 1.5 mg/dl. The histopathological features of acute rejection were absent in a second biopsy of the transplanted kidney. In summary, this case is an instance of monocyte-mediated acute rejection of a transplanted kidney.

Bisphosphonates and mortality in women with CKD and the presence or absence of cardiovascular disease.

BACKGROUND AND OBJECTIVES: A modest protective association between bisphosphonate prescription and mortality among women with CKD but without clinically manifest cardiovascular disease has been shown. Whether a prior cardiovascular event (myocardial infarction, stroke, or heart failure) modifies this association is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cohort of adult women with stages 3 and 4 CKD receiving primary care in a rural integrated health care system during the period 2004-2011 without history of advanced malignancy or organ transplantation (n=6756, median age=74 years, median follow-up=4.3 years) was retrospectively assembled. The primary analysis compared those patients prescribed bisphosphonates (both prevalent and incident use during follow-up) with those patients not prescribed. Additional approaches were taken to account for survival and indication biases. The primary outcome was time to death by Cox multivariable regression. RESULTS: In the primary analysis, compared with women not prescribed a bisphosphonate, the hazard ratio (95% confidence interval) for death among women prescribed a bisphosphonate was 0.90 (0.78 to 1.04) if there was no history of cardiovascular event but 1.22 (1.04 to 1.42) if there was history of cardiovascular event (P for interaction=0.004). In the additional approaches, associations between bisphosphonate prescription and mortality among those patients with a prior cardiovascular history varied: hazard ratios (95% confidence intervals) were 1.25 (1.01 to 1.57), 1.48 (1.16 to 1.88), and 0.94 (0.66 to 1.34). Interaction by prior cardiovascular event history varied across these three approaches (P=0.07, P=0.22, and P=0.05). CONCLUSION: In this study of women with CKD, the association between bisphosphonate treatment and mortality risk was inconclusive across a series of analyses designed to account for various types of selection and indication bias.

Fat-free weight prediction in morbidly obese females.

PURPOSE: Precise estimation of creatinine clearance in obese individuals relies on the appropriate assessment of lean body weight (LBW). Anthropometric methods of predicting LBW have not been validated in morbidly obese populations. PATIENTS AND METHODS: Using an existing dataset of anthropometric data for a female cohort with morbid obesity who had undergone measured FFW with dual energy absorptiometry, we evaluated the performance of five previously reported estimating equations for the prediction of LBW. Linear regression was used to derive a new LBW prediction formula and was then compared with the other formulae. RESULTS: Seventy females (mean [standard deviation] age, weight, and body mass index 43.0 [11.0] years, 128.1 [13.8] kg, and 48.3 [4.8] kg/m(2), respectively) were identified. LBW as estimated by the method of Garrow and Webster correlated well (r = 0.87) with measured mass while demonstrating the highest accuracy, best precision, and smallest bias (93%, 2.1 kg, and 2.9 kg, respectively; P < 0.0001 for all comparisons). The derived formula further improved bias, precision, and accuracy. CONCLUSION: Among females with morbid obesity, most previously reported estimating equations for LBW predicted FFW poorly. These findings have important clinical implications for the assessment of kidney function and for safe and effective drug dosing.

GFR decline and mortality risk among patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES: Estimates of the effect of estimated GFR (eGFR) decline on mortality have focused on populations with normal kidney function, or have included limited information on factors previously shown to influence the risk of death among patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We retrospectively assessed the effect of rate of eGFR decline on survival of patients with CKD receiving primary care through a large integrated health care system in central Pennsylvania between January 1, 2004, and December 31, 2009. RESULTS: A total of 15,465 patients were followed for a median of 3.4 years. Median rates of eGFR change by those in the lower, middle, and upper tertiles of eGFR slope were -4.8, -0.6, and 3.5 ml/min per 1.73 m(2)/yr, respectively. In Cox proportional hazard modeling for time to death, adjusted for baseline proteinuria, changes in nutritional parameters, and episodes of acute kidney injury during follow-up (among other covariates), the hazard ratio for those in the lower (declining) and upper (increasing) eGFR tertiles (relative to the middle, or stable, tertile) was 1.84 and 1.42, respectively. Longitudinal changes in nutritional status as well as episodes of acute kidney injury attenuated the risk only modestly. These findings were consistent across subgroups. CONCLUSIONS: eGFR change over time adds prognostic information to traditional mortality risk predictors among patients with CKD. The utility of incorporating eGFR trends into patient-risk assessment should be further investigated.

Acute cellular rejection predominated by monocytes is a severe form of rejection in human renal recipients with or without Campath-1H (alemtuzumab) induction therapy.

Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.