A Systematic Review of Reported Outcomes in ADPKD Studies.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic kidney disease. Studies of ADPKD presented results using different outcome measures. We aimed to summarize outcomes reported in ADPKD studies, including composite outcomes. Methods: We conducted a systematic review of published studies that included patients with ADPKD and measured kidney-related outcomes. We searched published databases and included all studies regardless of design with at least 100 participants for observational studies. We excluded studies that were limited to dialysis, transplant, or pregnancy outcomes in patients with ADPKD. Results: This review includes data from 175 published articles (49 randomized controlled trials, 2 interventional clinical trials, 30 post hoc analyses, and 94 observational studies). We identified 214 different outcomes, and we categorized them into the 24 main outcome domains. In addition, the review identified 13 articles that reported 9 different composite outcomes. Conclusion: The finding highlights the inconsistency in the outcomes reported by researchers and how they are measured in ADPKD studies. The variability in the outcomes reported supports the need to standardize outcomes in ADPKD studies.

A Computable Phenotype for Autosomal Dominant Polycystic Kidney Disease.

Background: A computable phenotype is an algorithm used to identify a group of patients within an electronic medical record system. Developing a computable phenotype that can accurately identify patients with autosomal dominant polycystic kidney disease (ADPKD) will assist researchers in defining patients eligible to participate in clinical trials and other studies. Our objective was to assess the accuracy of a computable phenotype using International Classification of Diseases 9th and 10th revision (ICD-9/10) codes to identify patients with ADPKD. Methods: We reviewed four random samples of approximately 250 patients on the basis of ICD-9/10 codes from the EHR from the Kansas University Medical Center database: patients followed in nephrology clinics who had ICD-9/10 codes for ADPKD (Neph+), patients seen in nephrology clinics without ICD codes for ADPKD (Neph-), patients who were not followed in nephrology clinics with ICD codes for ADPKD (No Neph+), and patients not seen in nephrology clinics without ICD codes for ADPKD (No Neph-). We reviewed the charts and determined ADPKD status on the basis of internationally accepted diagnostic criteria for ADPKD. Results: The computable phenotype to identify patients with ADPKD who attended nephrology clinics has a sensitivity of 99% (95% confidence interval [95% CI], 96.4 to 99.7) and a specificity of 84% (95% CI, 79.5 to 88.1). For those who did not attend nephrology clinics, the sensitivity was 97% (95% CI, 93.3 to 99.0), and a specificity was 82% (95% CI, 77.4 to 86.1). Conclusion: A computable phenotype using the ICD-9/10 codes can correctly identify most patients with ADPKD, and can be utilized by researchers to screen health care records for cohorts of patients with ADPKD with acceptable accuracy.

Analysis of the polycystin complex (PCC) in human urinary exosome-like vesicles (ELVs).

The polycystin-1 (PC1), polycystin-2 (PC2) and fibrocystin proteins, the respective products of the PKD1, PKD2 and PKHD1 genes, are abundant in urinary exosome-like vesicles (ELVs) where they form the polycystin complex (PCC). ELVs are 100 nm diameter membrane vesicles shed into the urine by the cells lining the nephron. Using MS/MS analysis of ELVs from individuals with PKD1 mutations and controls, we show that in addition to the well-described GPS/GAIN cleavage event in PC1 at 3048 aa and the proprotein convertase cleavage (PPC) event in fibrocystin at 3616 aa, there are multiple other cleavage events in these proteins. The C-terminal 11 transmembrane portion of PC1 undergoes three cleavage events in vivo. The absence of peptides from the C-terminal cytoplasmic tail of fibrocystin implies a cleavage event close to its single TM domain prior to loading onto the ELVs. There is also evidence that the C-terminal tail of PC2 is also cleaved in ELVs. Native gel analysis of the PCC shows that the entire complex is  > 2 MDa in size and that N-terminal GPS/GAIN cleaved PC1 and PPC cleaved fibrocystin ectodomains can be released under non-reducing conditions and resolve at 300 kDa. This paper shows that the three major human cystogene proteins are detectable in human urinary ELVs and that all three undergo post-translational proteolytic processing. Human urinary ELVs may be a useful source of material in the search for proteins that interact with the PCC.

Current Challenges in the Evaluation and Management of Hyponatremia.

BACKGROUND: Hyponatremia is a common electrolyte imbalance that clinicians face on a regular basis. SUMMARY: This review aims to discuss four current challenges that can arise when diagnosing and treating hyponatremia: low solute intake, heart failure, exercise-associated hyponatremia, and mild chronic hyponatremia. Low solute intake in a person who already has a urinary concentrating defect will lead to increased retention of free water. The free water retention will cause or worsen hyponatremia that is already present. Low solute intake is overlooked in patients with other disease processes that can cause hyponatremia, such as liver disease or heart failure. Heart failure and hyponatremia present their own set of challenges specifically with treatment as there are limited options. The newer class of aquaretics allows for the short-term treatment of hyponatremia. Exercise-associated hyponatremia is a phenomenon that has been described in ultra-endurance athletes. This happens when a person drinks a significant amount of water while exercising in the setting of antidiuretic hormone production from prolonged exercise. This acute drop in sodium must be treated with hypertonic saline. The term asymptomatic mild chronic hyponatremia is no longer valid. Mild chronic hyponatremia carries an increased risk of falls and fractures, specifically in the elderly populations. KEY MESSAGE: In summary, hyponatremia is a multifaceted disease and presents many challenges for physicians treating it.