Long-Term Administration of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND AND OBJECTIVES: In the 3-year Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 and 1-year Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trials, tolvaptan slowed the decline of eGFR in patients with autosomal dominant polycystic kidney disease at early and later stages of CKD, respectively. Our objective was to ascertain whether the reduction associated with the administration of tolvaptan is sustained, cumulative, and likely to delay the need for kidney replacement therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One hundred and twenty-eight patients with autosomal dominant polycystic kidney disease participated in clinical trials of tolvaptan at the Mayo Clinic. All had the opportunity to enroll into open-label extension studies. Twenty participated in short-term studies or received placebo only. The remaining 108 were analyzed for safety. Ninety seven patients treated with tolvaptan for ≥1 year (mean±SD, 4.6±2.8; range, 1.1-11.2) were analyzed for efficacy using three approaches: (1) comparison of eGFR slopes and outcome (33% reduction from baseline eGFR) to controls matched by sex, age, and baseline eGFR; (2) Stability of eGFR slopes with duration of follow-up; and (3) comparison of observed and predicted eGFRs at last follow-up. RESULTS: Patients treated with tolvaptan had lower eGFR slopes from baseline (mean±SD, -2.20±2.18 ml/min per 1.73 m2 per year) and from month 1 (mean±SD, -1.97±2.44 ml/min per 1.73 m2 per year) compared with controls (mean±SD, -3.50±2.09 ml/min per 1.73 m2 per year; P<0.001), and lower risk of a 33% reduction in eGFR (risk ratio, 0.63; 95% confidence interval, 0.38 to 0.98 from baseline; risk ratio, 0.53; 95% confidence interval, 0.31 to 0.85 from month 1). Annualized eGFR slopes of patients treated with tolvaptan did not change during follow-up and differences between observed and predicted eGFRs at last follow-up increased with duration of treatment. CONCLUSIONS: Follow-up for up to 11.2 years (average 4.6 years) showed a sustained reduction in the annual rate of eGFR decline in patients treated with tolvaptan compared with controls and an increasing separation of eGFR values over time between the two groups.

Cystatin C Predicts Renal Recovery Earlier Than Creatinine Among Patients With Acute Kidney Injury.

INTRODUCTION: Serum cystatin C increases earlier than creatinine during acute kidney injury. However, whether cystatin C decreases earlier during recovery is unknown. This retrospective study aimed to determine the temporal trend between creatinine and cystatin C in acute kidney injury. METHODS: We identified hospitalized patients with nonoliguric acute kidney injury who had serial creatinine and cystatin C values measured between May 2015 and May 2016. Demographic and laboratory data, causes of acute kidney injury, and relevant comorbidity data were collected through chart review. RESULTS: For the 63 identified patients, mean (SD) age was 58.7 (13.9) years; male sex, 62%; white race/ethnicity, 95%. Baseline median (range) creatinine was 1.1 (0.5-3.0) mg/dl; 13% were kidney transplant recipients and 37% received corticosteroids. Comorbidities included malignancy (38%), diabetes mellitus (33%), heart failure (19%), and thyroid disorder (16%). The cause of kidney injury was acute tubular necrosis in 71%, 61% had acute kidney injury stage III, and 33% required dialysis. Cystatin C began to decrease before creatinine in 68% of patients: 1 day earlier, 46%; 2 days earlier, 16%; and 3 days earlier, 6%. In 24% of cases, both began decreasing on the same day; in only 8%, cystatin C decreased after creatinine. Overall, cystatin C mean (95% confidence interval) decrease was 0.92 (0.65-1.18) days before creatinine (P < 0.001). CONCLUSION: In summary, cystatin C decreases before creatinine in most hospitalized patients with acute kidney injury. If confirmed in large prospective studies, these findings may have important management implications, possibly shortening hospital stay and reducing costs.

Younger Adults Initiating Hemodialysis: Antidepressant Use for Depression Associated With Higher Health Care Utilization.

OBJECTIVE: To examine associations between antidepressant use and health care utilization in young adults beginning maintenance hemodialysis (HD) therapy. PATIENTS AND METHODS: Antidepressant use, hospitalizations, and emergency department (ED) visits were examined in young adults (N=130; age, 18-44 years) initiating HD (from January 1, 2001, through December 31, 2013) at a midwestern US institution. Primary outcomes included hospitalizations and ED visits during the first year. RESULTS: Depression diagnosis was common (47; 36.2%) at HD initiation, yet only 28 patients (21.5%) in the cohort were receiving antidepressant therapy. The antidepressant use group was more likely to have diabetes mellitus (18 [64.3%] vs 33 [32.4%]), coronary artery disease (8 [28.6%] vs 12 [11.8%]), and heart failure (9 [32.1%] vs 15 [14.7%]) (P<.05 for all) than the untreated group. Overall, 68 (52.3%) had 1 or more hospitalizations and 33 (25.4%) had 1 or more ED visits in the first year. The risk of hospitalization during the first year was higher in the antidepressant use group (hazard ratio, 2.35; 95% CI, 1.39-3.96; P=.001), which persisted after adjustment for diabetes, coronary artery disease, and heart failure (hazard ratio, 1.94; 95% CI, 1.22-3.10; P=.006). Emergency department visit rates were similar between the groups. CONCLUSION: Depression and antidepressant use for mood indication are common in young adult incident patients initiating HD and and are associated with higher hospitalization rates during the first year. Further research should determine whether antidepressants are a marker for other comorbidities or whether treated depression affects the increased health care use in these individuals.

Autosomal Dominant Polycystic Kidney Patients May Be Predisposed to Various Cardiomyopathies.

INTRODUCTION: Mutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). Experimental evidence suggests an important role of the polycystins in cardiac development and myocardial function. To determine whether ADPKD may predispose to the development of cardiomyopathy, we have evaluated the coexistence of diagnoses of ADPKD and primary cardiomyopathy in our patients. METHODS: Clinical data were retrieved from medical records for patients with a coexisting diagnosis of ADPKD and cardiomyopathies evaluated at the Mayo Clinic (1984-2015). RESULTS: Among the 58 of 667 patients with available echocardiography data, 39 (5.8%) had idiopathic dilated cardiomyopathy (IDCM), 17 (2.5%) had hypertrophic obstructive cardiomyopathy, and 2 (0.3%) had left ventricular noncompaction. Genetic data were available for 19, 8, and 2 cases of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction, respectively. PKD1 mutations were detected in 42.1%, 62.5%, and 100% of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction cases, respectively. PKD2 mutations were detected only in IDCM cases and were overrepresented (36.8%) relative to the expected frequency in ADPKD (15%). In at least 1 patient from 3 IDMC families and 1 patient from a hypertrophic obstructive cardiomyopathy family, the cardiomyopathy did not segregate with ADPKD, suggesting that the PKD mutations may be predisposing factors rather than solely responsible for the development of cardiomyopathy. DISCUSSION: Coexistence of ADPKD and cardiomyopathy in our tertiary referral center cohort appears to be higher than expected by chance. We suggest that PKD1 and PKD2 mutations may predispose to primary cardiomyopathies and that genetic interactions may account for the observed coexistence of ADPKD and cardiomyopathies.

The Rate of Acute Kidney Injury After Total Hip Arthroplasty Is Low but Increases Significantly in Patients with Specific Comorbidities.

BACKGROUND: The purpose of this study was to investigate the rate and risk factors associated with the development of acute kidney injury after total hip arthroplasty, including the perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We retrospectively collected the demographic and comorbidity data of all patients who underwent total hip arthroplasty between 2004 and 2014 at our institution (n = 8,949). We conducted analyses of the entire cohort and a nested case-control subset. Subjects who developed acute kidney injury were matched by age, sex, and year of surgical procedure to subjects without acute kidney injury. Variables associated with acute kidney injury were determined using univariate and multivariate logistic regressions. RESULTS: The mean patient age (and standard deviation) was 64.6 ± 13.8 years, 48.6% of patients were male, and 114 cases (1.1%) developed acute kidney injury, mostly stage 1 (79%). Variables associated with acute kidney injury included older age (odds ratio [OR], 1.4 per decade; p < 0.001), male sex (OR, 1.78; p = 0.005), chronic kidney disease (OR, 4.6; p < 0.001), heart failure (OR, 4.5; p < 0.001), diabetes (OR, 2.1; p < 0.001), and hypertension (OR, 2.1; p = 0.007). The results were consistent in the case-control analysis. NSAIDs were not associated with acute kidney injury (OR, 1.26; p = 0.36), but were avoided in subjects at risk, making any interpretation difficult because of confounding. A risk model for acute kidney injury after total hip arthroplasty was developed for clinical use and had good discrimination (area under the curve, 0.82; p < 0.001). CONCLUSIONS: The rate of acute kidney injury after total hip arthroplasty is low, but increases significantly, from <1% to >20%, in those with several independent risk factors present preoperatively. Increasing awareness of these risk factors may help to decrease the risk of acute kidney injury after total hip arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Renal Outcomes in Patients With IgA Nephropathy Undergoing Liver Transplant: A Retrospective Cohort Study.

BACKGROUND: End-stage liver disease (ESLD) is the most common cause of secondary immunoglobulin A nephropathy (IgAN). Multiple mechanisms have been proposed to explain the association between liver disease and IgAN. Although some mechanisms are expected to reverse in patients after liver transplant, the long-term renal prognosis is unclear for these patients. METHODS: This observational retrospective cohort study examined the renal outcomes of 14 patients who had IgAN with end-stage liver disease and subsequently underwent either liver transplant alone or combined liver and kidney transplant at a single tertiary care center. RESULTS: Of the 7 patients who underwent liver transplant alone, hematuria persisted in 2, 4 had progressive loss of kidney function with worsening proteinuria in 3 but only 1 reached end-stage renal disease 5 years posttransplant. Among 7 combined liver and kidney transplant recipients, 1 had histologic and 1 had histologic and clinical recurrence of IgAN without kidney allograft loss. CONCLUSIONS: IgAN in patients with advanced liver disease does not necessarily resolve after liver transplant but has overall favorable renal outcomes.

Charcoal hemoperfusion in the treatment of medically refractory pruritus in cholestatic liver disease.

BACKGROUND: Pruritus is a distressing symptom in a considerable proportion of cholestatic patients and a few of them do not respond to conventional treatment. Charcoal hemoperfusion (CH) is an extracorporeal technique that is effective in eliminating protein-bound substances which may have accumulated during cholestasis. Several case reports have shown significant reduction of bilirubin in mechanical jaundice and neonatal hemolytic jaundice. However, the published data of CH for the treatment of refractory pruritus in cholestatic patients are scarce. METHODS: Procedure code "Charcoal hemoperfusion" (90997) was used to identify patients who received CH at Mayo Clinic, Rochester, from 1 January 2000 to 5 January 2015. Patients who received CH for refractory cholestatic pruritus were retrospectively reviewed. RESULTS: Thirteen patients were identified. A median of 5 (range 1-18) sessions for a total of 20 (1-72) h were performed. CH resulted in a significant decrease of pruritus in nine patients (69%). Two patients did not have significant relief and two patients did not pursue further treatments after having adverse reactions during the first session. Median pruritus numerical rating scale significantly decreased from 9/10 (9-10) to 4/10 (0-9) post-treatment (p = 0.004). Duration of symptom-free periods ranged from 8 to 90 days (median 18 days) in six patients who returned for follow-up. Most common adverse reactions were pain, bleeding from the catheter site and fever. CONCLUSION: CH temporarily improves the severity of medically refractory cholestatic pruritus in some patients. However, the improvement is not sustained and the short duration of benefit should be balanced with the invasive nature of the therapy and the relatively common adverse reactions.

Survival, Risk Factors, and Effect of Treatment in 101 Patients With Calciphylaxis.

OBJECTIVE: To report on the survival and the associations of treatments upon survival of patients with calciphylaxis seen at a single center. PATIENTS AND METHODS: Using the International Classification of Diseases, Ninth Revision diagnosis code of 275.49 and the keyword "calciphylaxis" in the dismissal narrative, we retrospectively identified 101 patients with calciphylaxis seen at our institution between January 1, 1999, through September 20, 2014, using a predefined, consensus-developed classification scheme. RESULTS: The average age of patients was 60 years: 81 (80.2%) were women; 68 (68.0%) were obese; 19 (18.8%) had stage 0 to 2 chronic kidney disease (CKD), 19 (18.9%) had stage 3 or 4 CKD; 63 (62.4%) had stage 5 or 5D (dialysis) CKD. Seventy-five patients died during follow-up. Six-month survival was 57%. Lack of surgical debridement was associated with insignificantly lower 6-month survival (hazard ratio [HR]=1.99; 95% CI, 0.96-4.15; P=.07) and significantly poorer survival for the entire duration of follow-up (HR=1.98; 95% CI, 1.15-3.41; P=.01), which was most pronounced in stage 5 or 5D CKD (HR=1.91; 95% CI, 1.03-3.56; P=.04). Among patients with stage 5/5D CKD, subtotal parathyroidectomy (performed only in patients with hyperparathyroidism) was associated with better 6-month (HR=0.12; 95% CI, 0.02-0.90; P=.04) and overall survival (HR= 0.37; 95% CI, 0.15-0.87; P=.02). CONCLUSION: Calciphylaxis is associated with a high mortality rate. Significantly effective treatments included surgical debridement and subtotal parathyroidectomy in patients with stage 5/5D CKD with hyperparathyroidism. Treatments with tissue-plasminogen activator, sodium thiosulfate, and hyperbaric oxygen therapy were not associated with higher mortality.

Calciphylaxis: A Disease of Pannicular Thrombosis.

OBJECTIVE: To identify coagulation risk factors in patients with calciphylaxis and the relationship between anticoagulation use and overall survival. PATIENTS AND METHODS: Study subjects were 101 patients with calciphylaxis seen at Mayo Clinic from 1999 to September 2014. Data including thrombophilia profiles were extracted from the medical records of each patient. Survival status was determined using patient registration data and the Social Security Death Index. Survival was estimated using the Kaplan-Meier method, and associations were evaluated using Cox proportional hazards models. RESULTS: Sixty-four of the 101 patients underwent thrombophilia testing. Of these, a complete test panel was performed in 55 and a partial panel in 9. Severe thrombophilias observed in 60% (33 of 55) of the patients included antiphospholipid antibody syndrome protein C, protein S, or antithrombin deficiencies or combined thrombophilias. Of the 55 patients, severe thrombophilia (85%, 23 of 27) was noted in patients who were not on warfarin at the time of testing (27). Nonsevere thrombophilias included heterozygous factor V Leiden (n=2) and plasminogen deficiency (n=1). For the comparison of survival, patients were divided into 3 treatment categories: Warfarin (n=63), other anticoagulants (n=20), and no anticoagulants (n=18). There was no statistically significant survival difference between treatment groups. CONCLUSION: Laboratory testing reveals a strikingly high prevalence of severe thrombophilias in patients with calciphylaxis, underscoring the importance of congenital and acquired thrombotic propensity potentially contributing to the pathogenesis of this disease. These findings may have therapeutic implications; however, to date, survival differences did not vary by therapeutic choice.

Effect of genotype on the severity and volume progression of polycystic liver disease in autosomal dominant polycystic kidney disease.

BACKGROUND: The autosomal dominant polycystic kidney disease (APDKD) genotype influences renal phenotype severity but its effect on polycystic liver disease (PLD) is unknown. Here we analyzed the influence of genotype on liver phenotype severity. METHODS: Clinical data were retrieved from electronic records of patients who were mutation screened with the available liver imaging (n = 434). Liver volumes were measured by stereology (axial or coronal images) and adjusted to height (HtLV). RESULTS: Among the patients included, 221 (50.9%) had truncating PKD1 (PKD1-T), 141 (32.5%) nontruncating PKD1 (PKD1-NT) and 72 (16.6%) PKD2 mutations. Compared with PKD1-NT and PKD2, patients with PKD1-T had greater height-adjusted total kidney volumes (799 versus 610 and 549 mL/m; P < 0.001). HtLV was not different (1042, 1095 and 1058 mL/m; P = 0.64) between the three groups, but females had greater HtLVs compared with males (1114 versus 1015 mL/m; P < 0.001). Annualized median liver growth rates were 1.68, 1.5 and 1.24% for PKD1-T, PKD1-NT and PKD2 mutations, respectively (P = 0.49), and remained unaffected by the ADPKD genotype when adjusted for age, gender and baseline HtLV. Females <48 years of age had higher annualized growth rates compared with those who were older (2.65 versus 0.09%; P < 0.001). After age 48 years, 58% of females with severe PLD had regression of HtLV, while HtLV continued to increase in males. CONCLUSIONS: In contrast to the renal phenotype, the ADPKD genotype was not associated with the severity or growth rate of PLD in ADKPD patients. This finding, along with gender influence, indicates that modifiers beyond the disease gene significantly influence the liver phenotype.

Volume regression of native polycystic kidneys after renal transplantation.

BACKGROUND: The natural course of native kidneys after renal transplantation (RT) or dialysis in patients with autosomal dominant polycystic kidney disease (ADPKD) remains poorly understood. METHODS: We measured the total volumes of native kidneys and liver in 78 and 68 ADPKD patients, respectively, who had pre-transplant (within 2 years) and at least one post-transplant computed tomography (CT)/magnetic resonance imaging (MRI); in 40 patients with at least two post-transplant but no pre-transplant CT/MRIs; in 9 patients on chronic hemodialysis with at least one CT/MRI before and after beginning dialysis; and in 5 patients who had no image before and more than one image after dialysis. The last imaging was used in patients with multiple studies. RESULTS: Mean total kidney volume (TKV) ( ± SD) prior to transplantation was 3187 ± 1779 mL in the 78 patients who had imaging before and after transplantation and decreased by 20.2, 28.6, 38.3 and 45.8% after 0.5-1 (mean 0.7), 1-3 (1.8), 3-10 (5.7) and >10 (12.6) years, respectively. In the multivariable analysis, time on dialysis prior to RT and time from baseline to transplantation were negatively associated with reduction in TKV, whereas estimated glomerular filtration rate (eGFR) after transplantation and time from transplantation were positively associated with percent reduction in TKV. In the 40 patients with imaging only after transplantation, TKV decreased by 3.2 ± 16.3% between 7.2 ± 6.0 and 11.2 ± 6.8 years after transplantation (P < 0.001). TKV was 11.2 ± 35.6% higher (P = NS) after a follow-up of 3.4 ± 2.0 years in the 9 patients with imaging before and after initiation of hemodialysis and 3.4 ± 40.2% lower (P = NS) in the 5 patients with imaging between 2.0 ± 2.1 and 3.5 ± 3.6 years after initiation of hemodialysis. In the 68 patients with liver measurements, volume increased by 5.8 ± 17.9% between baseline and follow-up at 3.7 ± 3.8 years after transplantation (P = 0.009). CONCLUSIONS: TKV of native polycystic kidneys decreases substantially after RT. The reduction occurs mainly during the early post-transplantation period and more slowly thereafter.

Extracorporeal Elimination of Piperacillin/Tazobactam during Molecular Adsorbent Recirculating System Therapy.

Use of the Molecular Adsorbent Recirculating System (MARS) as a liver support device continues to grow worldwide. Various components of the MARS circuit remove both protein-bound and water-soluble molecules. Little is known about the extent of the enhanced clearance mechanisms used in MARS therapy on drug elimination. Of particular interest to acute care practitioners is the impact of MARS on antibiotic clearance, as suboptimal concentrations of such drugs can negatively impact patient outcomes. The properties of piperacillin/tazobactam suggest that elimination may be enhanced in the setting of MARS therapy. We describe two cases in which this was studied. Piperacillin concentrations were determined at various points within the MARS circuit, and patient serum concentrations were reported throughout the dosing interval while receiving MARS therapy. Piperacillin concentrations in both cases were in excess of the desired goal minimum inhibitory concentrations for treatment of gram-negative infections. Use of an extended-infusion strategy of piperacillin/tazobactam 3.375 or 4.5 g given every 8 hours maintained desired serum levels throughout the dosing interval. To our knowledge, this is the second published report on the use of piperacillin/tazobactam during MARS therapy. These case reports reveal successful dosing strategies for patients requiring piperacillin/tazobactam while receiving MARS therapy, as well as quantify the influence of individual MARS elements on drug extraction.

Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials.

The rate of renal disease progression varies widely among patients with autosomal dominant polycystic kidney disease (ADPKD), necessitating optimal patient selection for enrollment into clinical trials. Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic resonance images and three or more eGFR measurements over ≥6 months were classified radiologically as typical (n=538) or atypical (n=52). Total kidney volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe). Typical patients were randomly partitioned into development and internal validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges for age (1A-1E, in increasing order). Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external validation. TKVe correlated strongly with TKVs, without systematic underestimation or overestimation. A longitudinal mixed regression model to predict eGFR decline showed that log2HtTKV and age significantly interacted with time in typical patients, but not in atypical patients. When 1A-1E classifications were used instead of log2HtTKV, eGFR slopes were significantly different among subclasses and, except for 1A, different from those in healthy kidney donors. The equation derived from the development set predicted eGFR in both validation sets. The frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort. Class and subclass designations were stable. An easily applied classification of ADPKD based on HtTKV and age should optimize patient selection for enrollment into clinical trials and for treatment when one becomes available.

Native Nephrectomy in Renal Transplant Recipients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Native nephrectomy (NNx) is often done in patients with autosomal dominant polycystic kidney disease (ADPKD). Controversy exists concerning the need and timing of nephrectomy in transplant candidates. We hypothesize that post-transplant NNx does not negatively impact patient and graft survival. METHODS: Among 470 ADPKD transplant recipients included in the study, 114 (24.3%) underwent pre- (30.7%) or post-transplant (69.3%) NNx. Clinical data was retrieved from electronic records. Follow up was until death, graft loss or June 2014. Perioperative complications were compared between the surgical techniques (open or laparoscopic) and between the pre- and post-transplant nephrectomy groups. The effect of nephrectomy on graft survival was analyzed as a time-dependent covariate when performed post-transplant. RESULTS: Mean age at transplant was 52.4 years, 53.8% were male, 93% white, 70% were from living donors and 56.8% were pre-emptive. Nephrectomy was done laparoscopically in 31% and 86% in the pre- and post- transplant nephrectomy groups, respectively. Complications were less common in those who underwent nephrectomy post-transplant (26.6% vs. 48%, p=0.03) but were similar regardless of surgical technique (open, 33.3% vs. laparoscopic 33%, p=0.66). Patient and graft survival were similar between those who underwent pre-transplant nephrectomy and the rest of the recipients. In the post-transplant nephrectomy group, nephrectomy did not affect patient (HR 0.77, CI 0.38-1.54, p=0.45) or graft survival (HR 1.0, CI 0.57-1.76, p=0.1). CONCLUSIONS: Nephrectomy does not adversely affect patient or graft survival. Post-transplant nephrectomy is feasible when indicated without compromising long term graft outcome and has fewer complications than pre-transplant nephrectomy.

Cardiovascular disease burden and risk factors before and after kidney transplant.

Cardiovascular (CV) disease is the most common cause of mortality among kidney transplant candidates on the waiting-list and after kidney transplantation. The mechanisms of cardiovascular disease burden after transplant are multifactorial and the risk is largely determined by pre-transplant factors including CV disease and dialysis duration. Current pre-transplant cardiac evaluation protocols have proven to be inconsistent in predicting adverse cardiovascular outcome post-transplant. However, multiple biomarkers have been recognized as predictors of all-cause mortality and cardiovascular events including graft function, hemoglobin, homocysteine, C - reactive protein among others. Of these, elevation in the biomarker cardiac troponin T appears to be a significant predictor of cardiovascular events and mortality among wait-listed kidney transplant candidates and after transplantation. The relationship between CV risk reduction, normalization of cardiac troponin T levels and restoration of renal function after kidney transplant is complex but opens opportunities for the use of cardiac troponin T and other cardiovascular biomarkers as important endpoints of clinical interventions in kidney transplant recipients.

Rapid self-infusion of tap water.

Intravenous self-infusion of tap water has never been reported in the literature.  We present a 24-year-old healthy man who self-administered 2.5 L of tap water over 2 hours and developed acute illness including fever, change of mental status, acute hemolysis, low-grade disseminated intravascular coagulation, and acute kidney injury.  

Severe anion gap metabolic acidosis from acetaminophen use secondary to 5-oxoproline (pyroglutamic acid) accumulation.

Anion gap metabolic acidosis (AGMA) is commonly encountered in medical practice. Acetaminophen-induced AGMA is, however, not widely recognized. We report 2 cases of high anion gap metabolic acidosis secondary to 5-oxoproline accumulation resulting from acetaminophen consumption: the first case caused by acute one-time ingestion of large quantities of acetaminophen and the second case caused by chronic repeated ingestion in a patient with chronic liver disease. Recognition of this entity facilitated timely diagnosis and effective treatment. Given acetaminophen is commonly used over the counter medication, increased recognition of this adverse effect is of important clinical significance.

Urolithiasis and the risk of ESRD.

BACKGROUND AND OBJECTIVES: The contribution of urolithiasis, if any, to the development of ESRD is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All stone formers in Olmsted County, Minnesota, first diagnosed between 1984 and 2008 were identified by diagnostic codes with up to four controls matched on age and sex. Charts were reviewed to validate symptomatic stone formers in a random subset. Incident ESRD events were identified by the US Renal Data System. RESULTS: Altogether, 51 stone formers and 75 controls developed ESRD among 6926 stone formers and 24,620 matched controls followed for a mean of 9 years. Stone formers had an increased risk of ESRD after adjusting for diabetes, hypertension, dyslipidemia, gout, and CKD (hazard ratio: 2.09; 95% confidence interval: 1.45-3.01). This increased risk of ESRD remained in the subset of 2457 validated symptomatic stone formers (hazard ratio: 1.95; 95% confidence interval: 1.09-3.49). The attributable risk of ESRD from symptomatic urolithiasis was 5.1% based on a prevalence of 5.4% for stone formers. For stone formers versus controls who developed ESRD, there was an increased likelihood of past hydronephrosis (44% versus 4%), recurrent urinary tract infections (26% versus 4%), acquired single kidney (15% versus 3%), neurogenic bladder (12% versus 1%), and ileal conduit (9% versus 0%), but not diabetes (32% versus 49%) or hypertension (44% versus 52%). CONCLUSIONS: Symptomatic stone formers are at increased risk for ESRD independent of several cardiovascular risk factors. Other urological disease is relatively common among stone formers who develop ESRD.

Renal histological lesions and outcome in liver transplant recipients.

BACKGROUND: Chronic kidney disease in liver transplant (OLT) recipients is often attributed to calcineurin inhibitors (CNI) toxicity, but little is known about the spectrum of their renal histological lesions. METHODS: Between 1988 and 2008, 1698 OLTs were performed in our center. We retrospectively analyzed clinical and histological data on 23 recipients (1.4%) referred for kidney biopsy (KB). RESULTS: Median age at OLT was 50.2 yr, 65.2% were men, 30.4% had hepatitis C, and 95.7% were given CNI. KB was performed 6.9 yr (median) post-OLT. Median creatinine was 1 mg/dL pre-OLT and 2.2 mg/dL at KB. Main pathological diagnoses were focal segmental and global glomerulosclerosis (n = 8, 34.8%), glomerular diseases (7, 30.4%), CNI toxicity (2, 8.7%), and diabetic nephropathy (2, 8.7%). Moderate/severe interstitial fibrosis, tubular atrophy, arteriosclerosis, and hyalinosis were present in 47.8%, 43.5%, 60.9%, and 56.5%, respectively. Twelve patients (52.5%) reached end-stage renal disease (ESRD) and 17 (73.9%) died. Death was more common among those reaching ESRD, but the difference was not significant (83.3% vs. 63.6%, p = 0.37). CONCLUSION: Renal histology is variable and not limited to CNI toxicity in OLT recipients referred for KB. Whether management based on KB findings can directly improve outcomes remains unclear.

Recurrent idiopathic membranous nephropathy: early diagnosis by protocol biopsies and treatment with anti-CD20 monoclonal antibodies.

Membranous nephropathy (MN) recurs posttransplant in 42% of patients. We compared MN recurrence rates in a historical cohort transplanted between 1990 and 1999 and in a current cohort diagnosed by protocol biopsies, we analyzed the progression of the disease and we assessed the effects of anti-CD20 antibodies (Rituximab) on recurrent MN. The incidence of recurrent MN was similar in the historical (53%) and the current cohorts (41%), although in the later the diagnosis was made earlier (median, 4[2-21] months vs. 83[6-149], p = 0.002) and the disease was clinically milder. Twelve out of 14 patients (86%) with recurrent MN in the current cohort had progressive increases in proteinuria. Eight recipients were treated with Rituximab after their proteinuria increased from median, 211 mg/day (64-4898) at diagnosis to 4489 (898-13 855) (p = 0.038). Twelve months post-Rituximab, 75% of patients had either partial (PR) or complete remission (CR). After 24 months 6/7 (86%) had PR/CR and one patient relapsed. Posttreatment biopsies showed resorption of electron dense immune deposits in 6/7 cases and were negative for C3 (4/7) and IgG (3/7). Protocol biopsies allow early diagnosis of subclinical recurrent MN, which is often progressive. Treatment of recurrent MN with Rituximab is promising and should be evaluated in a prospective randomized controlled trial.