Effects of tolvaptan discontinuation in patients with autosomal dominant polycystic kidney disease: a post hoc pooled analysis.

BACKGROUND: Tolvaptan slows kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD) who are at risk of rapid progression. Given that treatment requires commitment to long-term use, we evaluated the effects of tolvaptan discontinuation on the trajectory of ADPKD progression. METHODS: This was a post hoc analysis of pooled data from two clinical trials of tolvaptan (TEMPO 2:4 [NCT00413777] and TEMPO 3:4 [NCT00428948]), an extension trial (TEMPO 4:4 [NCT01214421]), and an observational study (OVERTURE [NCT01430494]) that enrolled patients from the other trials. Individual subject data were linked longitudinally across trials to construct analysis cohorts of subjects with a tolvaptan treatment duration > 180 days followed by an off-treatment observation period of > 180 days. For inclusion in Cohort 1, subjects were required have ≥ 2 outcome assessments during the tolvaptan treatment period and ≥ 2 assessments during the follow-up period. For Cohort 2, subjects were required to have ≥ 1 assessment during the tolvaptan treatment period and ≥ 1 assessment during the follow-up period. Outcomes were rates of change in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). Piecewise-mixed models compared changes in eGFR or TKV in the on-treatment and post-treatment periods. RESULTS: In the Cohort 1 eGFR population (n = 20), the annual rate of eGFR change (in mL/min/1.73 m2) was -3.18 on treatment and -4.33 post-treatment, a difference that was not significant (P = 0.16), whereas in Cohort 2 (n = 82), the difference between on treatment (-1.89) and post-treatment (-4.94) was significant (P < 0.001). In the Cohort 1 TKV population (n = 11), TKV increased annually by 5.18% on treatment and 11.69% post-treatment (P = 0.06). In Cohort 2 (n = 88), the annual TKV growth rates were 5.15% on treatment and 8.16% post-treatment (P = 0.001). CONCLUSIONS: Although limited by small sample sizes, these analyses showed directionally consistent acceleration in measures of ADPKD progression following the discontinuation of tolvaptan.

Renal Genetics Clinic: 3-Year Experience in the Cleveland Clinic.

Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury.

BACKGROUND: Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. METHODS: The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. RESULTS: The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. CONCLUSIONS: In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.

Transperitoneal Robot-assisted Partial Nephrectomy with Minimum Follow-up of 5 Years: Oncological and Functional Outcomes from a Single Institution.

BACKGROUND: Robot-assisted partial nephrectomy (RAPN) is an established, minimally invasive nephron-sparing technique with excellent perioperative and intermediate oncological outcomes. However, long-term oncological outcomes have not been reported to date. OBJECTIVE: To report oncological and functional outcomes of RAPN among patients with minimum follow-up of 5 yr. DESIGN, SETTING, AND PARTICIPANTS: Data for consecutive patients undergoing RAPN since October 2006 were extracted from a prospectively-maintained institutional PN database. Patients with benign tumors, genetic mutations, prior radical or ipsilateral PN, and those with follow-up of <5 yr were excluded. INTERVENTION: Transperitoneal RAPN for renal cell carcinoma (RCC). OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Demographic, perioperative, postoperative, functional, and oncological data were evaluated. A linear random-effects model was used to estimate the effect of follow-up duration on the estimated glomerular filtration rate (eGFR) after adjustment for potential confounders. Univariable competing-risks regression analyses were performed to evaluate the hazard ratio (HR) for cancer-related events for the variables of interest. RESULTS AND LIMITATIONS: A total of 278 RAPNs for RCC were included. eGFR was significantly lower at follow-up time points than at baseline. At last follow-up (median 46 mo, interquartile range 30-58) the mean eGFR difference was -10.6ml/min (95% confidence interval -12.56 to -8.66; p < 0.0001). There were 28 deaths (10.1%) in the cohort during the follow-up period, of which five (1.8%) were related to metastatic RCC. The 5-yr and 7-yr cumulative incidence of RCC deaths was 1.80% at both 5 and 7 yr, while the cumulative incidence of local recurrence was 3.61% and 4.16%, and that of metastasis was 3.24% and 4.57% at 5 and 7 yr, respectively. Univariable competing-risks regression revealed that higher Fuhrman grade (HR 8.76; p = 0.051), larger tumor size (HR 1.67; p < 0.0001), and tumor necrosis (HR 16.73; p = 0.0019) were independent predictors of RCC death. The retrospective design and potential selection bias due to patient selection in the early RAPN experience may limit the generalizability of the findings. CONCLUSIONS: This is the first study reporting minimum oncological follow-up of 5 yr after RAPN. The results demonstrate excellent long-term oncological outcomes after RAPN in a selected cohort of patients. Our data confirm that the renal functional deterioration after RAPN remains stable over time after the early postoperative decrease. PATIENT SUMMARY: Robot-assisted partial nephrectomy is being more widely used as a standard treatment for small localized renal cell carcinomas. This study reveals excellent long-term cancer control for both local recurrences and distant metastases. Renal function is stable after an initial postoperative deterioration.

Diagnostic Performance of Blood Pressure Measurement Modalities in Living Kidney Donor Candidates.

BACKGROUND AND OBJECTIVES: Precise BP measurement to exclude hypertension is critical in evaluating potential living kidney donors. Ambulatory BP monitoring is considered the gold standard method for diagnosing hypertension, but it is cumbersome to perform. We sought to determine whether lower BP cutoffs using office and automated BP would reduce the rate of missed hypertension in potential living donors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured BP in 578 prospective donors using three modalities: (1) single office BP, (2) office automated BP (average of five consecutive automated readings separated by 1 minute), and (3) ambulatory BP. Daytime ambulatory BP was considered the gold standard for diagnosing hypertension. We assessed both the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) and the American College of Cardiology/American Heart Association (ACC/AHA) definitions of hypertension in the cohort. Empirical thresholds of office BP and automated BP for the detection of ambulatory BP-diagnosed hypertension were derived using Youden index, which maximizes the sum of sensitivity and specificity and gives equal weight to false positive and false negative values. RESULTS: Hypertension was diagnosed in 90 (16%) prospective donors by JNC-7 criteria and 198 (34%) prospective donors by ACC/AHA criteria. Masked hypertension was found in 3% of the total cohort by JNC-7 using the combination of office or automated BP, and it was seen in 24% by ACC/AHA guidelines. Using Youden index, cutoffs were derived for both office and automated BP using JNC-7 (<123/82 and <120/78 mm Hg) and ACC/AHA (<119/79 and <116/76 mm Hg) definitions. Using these lower cutoffs, the sensitivity for detecting hypertension improved from 79% to 87% for JNC-7 and from 32% to 87% by ACC/AHA definition, with negative predictive values of 95% and 87%, respectively. Missed (masked) hypertension was reduced to 2% and 4% of the entire cohort by JNC-7and ACC/AHA, respectively. CONCLUSIONS: The prevalence of hypertension was higher in living donor candidates using ACC/AHA compared JNC-7 definitions. Lower BP cutoffs in the clinic improved sensitivity and led to a low overall prevalence of missed hypertension in prospective living kidney donors.

Perioperative, oncological and functional outcomes after robotic partial nephrectomy vs. cryoablation in the elderly: A propensity score matched analysis.

OBJECTIVE: To compare perioperative, oncological and functional outcomes of robotic partial nephrectomy (RPN) versus cryoablation in elderly patients (>75 years old), accounting for patient's and tumor's related factors. METHODS: Retrospective institutional review of 312 consecutive elderly patients (> 75 years old) who underwent RPN or cryoablation for renal mass (June 2006-December 2016). Demographic, perioperative, functional, and oncological data were evaluated. Sixty-five patients who underwent RPN were propensity-score matched 1:1 to 65 who underwent cryoablation (matching was based on demographics, renal function, comorbidities and tumor characteristics). Perioperative outcomes were compared. Survival analysis was performed to estimate overall (OS), recurrence-free (RFS) and cancer-specific survival (CSS) by Kaplan-Meier method. A linear mixed effect model (LME) estimated the effect of follow-up on estimated glomerular filtration rate (eGFR). RESULTS: After matching, the variables were well balanced with no differences at baseline between groups. Shorter operative time and lower blood losses favored cryoablation (140 vs. 200 min, P < 0.0001 and 100 vs. 195 ml, P = 0.0002, respectively). Overall complications rate was higher for RPN (31% vs. 9%; P = 0.007), but no difference was found in major (Clavien III-IV) complications (6% vs. 1.5%, P = 0.2). At a median follow-up of 37 (29-44) and 46 (38-53) months for RPN and cryoablation, no significant differences were found in CSS (100% vs. 95%, P = 0.3) and OS (80% vs. 75%, P = 0.2) but RFS was higher for RPN (100% vs. 83%, RPN vs. cryoablation, respectively, P = 0.02). eGFR was comparable between the groups at every time point analyzed. CONCLUSIONS: Although with a higher rate of recurrences, our data confirm cryoablation as a lower morbidity profile treatment option for small renal masses in the elderly population, with cancer-specific survival comparable to surgery.

Cold ischemia technique during robotic partial nephrectomy: a propensity score-matched comparison with open approach.

BACKGROUND: Open ice slush for renal cooling during partial nephrectomy (PN) has been reproduced during robotic PN (RPN). The aim of this study was to compare the perioperative and functional outcomes between RPN and open PN (OPN) using a cold ischemia technique. METHODS: Consecutive patients undergoing PN using cold ischemia technique were extracted from our prospectively-maintained database (2007-2016). RPN and OPN patients were 1:2 propensity-score (PS) matched via a greedy algorithm. The balance of the baseline variables was checked for the matched cohorts. Perioperative and functional outcomes were compared. RESULTS: Fifty-one RPN and 334 OPN using cold ischemia were extracted. After PS adjustments, 51 RPN vs. 102 OPN with no significant differences in baseline features were compared. Regarding perioperative outcomes, blood loss (100 mL [IQR 50; 200] vs. 260 mL [IQR 200; 350], <0.001), postoperative complications rate (10 patients (19.6%) vs. 38 patients (37.3%), P=0.027) and hospital stay (3 days [IQR 2; 4] vs. 5 days [IQR 4; 6], P<0.001) favored RPN. Renal functional outcomes were comparable at repeated measures analysis. CONCLUSIONS: In our experience, cold ischemia technique can be effectively reproduced during RPN, with a potential advantage in terms of blood loss, complications rate and hospital stay over the traditional OPN procedure.

Cold Versus Warm Ischemia Robot-Assisted Partial Nephrectomy: Comparison of Functional Outcomes in Propensity-Score Matched "At Risk" Patients.

OBJECTIVES: To compare functional outcomes of warm ischemia RPN (wRPN) to cold ischemia RPN (cRPN) in "at risk" patients. MATERIALS AND METHODS: Retrospective review of institutional database queried for all patients who underwent cRPN/wRPN (January 2007-December 2016). For the study purpose, patients with solitary kidney and/or history of partial nephrectomy and/or multiple tumors and/or preoperative estimated Glomerular Filtration Rate (eGFR) <60 mL/minute were extracted. To reduce inherent biases, groups were matched on key variables related to renal function through a greedy matching algorithm with no replacement. Renal functional outcomes were evaluated by eGFR drops at 1-3 days and at 1, 3, 6, and 12 months postoperatively. A linear mixed effects model was used to assess eGFR at each follow-up who received either cRPN or wRPN. Follow-up was treated as a factor variable to account for nonlinear time trends. Contrast analysis was used to compare cRPN vs wRPN groups at each follow-up, using Sidak-Holm p-value adjustments for multiple comparisons. RESULTS: Out of 19 cRPN patients and 279 wRPN patients, 14 cRPN patients were finally matched 1:1 with no replacement to 14 wRPN. There was no significant difference in preoperative eGFR for matched patients undergoing cRPN vs wRPN. Since the first postoperative day, cRPN patients had higher eGFR. The difference was statistically significant since the third month postoperatively (mean difference = 18.201, 95% confidence interval [CI]: 1.930-34.472) and remained at both the sixth month (mean difference = 18.839, 95% CI: 2.568-35.109) and the 12th month (mean difference = 21.277, 95% CI: 5.006-37.547) follow-up. CONCLUSIONS: Accounting for unmodifiable and modifiable factors, in a cohort of highly selected patients "at risk" for postoperative significant decline in renal function after RPN, renal functional outcomes appear to be superior with cold ischemia technique.

Impact of Intensive Versus Standard Blood Pressure Management by Tertiles of Blood Pressure in SPRINT (Systolic Blood Pressure Intervention Trial).

Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 [T1], <132; tertile 2 [T2], 132-145; and tertile 3 [T3], >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction (P=0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles-a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP.

Baseline blood pressure control in Hispanics: characteristics of Hispanics in the Systolic Blood Pressure Intervention Trial.

The Systolic Blood Pressure Intervention Trial (SPRINT) tested whether a systolic blood pressure (SBP) value <120 mm Hg reduces adverse clinical outcomes compared with the goal of <140 mm Hg. Here the authors describe the baseline characteristics of Hispanic participants in SPRINT. Nondiabetic hypertensive patients 50 years and older with SBP 130-180 mm Hg taking zero to four blood pressure (BP) medications were enrolled from the mainland United States and Puerto Rico. Cross-sectional, bivariate analysis was employed comparing sociodemographic and clinical factors in Hispanics vs non-Hispanics. Multivariable logistic regression models restricted to Hispanics were used to identify factors associated with achieved BP control (SBP <140 mm Hg and diastolic BP <90 mm Hg) at baseline. Eleven percent (n=984) of SPRINT participants were Hispanic; 56% (n=549) of Hispanics were living in Puerto Rico and the remainder were living on the US mainland. Hispanics overall were younger, more often female, less likely to live alone, and more likely to have lower education and be uninsured, although just as likely to be employed compared with non-Hispanics. BP control was not different between Hispanics vs non-Hispanics at baseline. However, a significantly higher percentage of Hispanics on the US mainland (compared with Hispanics in Puerto Rico) had controlled BP. BP control was independently associated with cardiovascular disease history and functional status among Hispanics, specifically those living in Puerto Rico, whereas functional status was the only independent predictor of BP control identified among mainland Hispanics. These findings highlight the diversity of the SPRINT population. It remains to be seen whether factors identified among Hispanics impact intervention goals and subsequent clinical outcomes.