American Journal of Kidney Diseases最新文献

Rationale & objective: Monoallelic predicted Loss-of-Function (pLoF) variants in IFT140 have recently been associated with an autosomal dominant polycystic kidney disease (ADPKD)-like phenotype. This study sought to enhance the characterization of this phenotype.

Study design: Case series.

Setting & participants: Seventy-five among 2797 European individuals with ADPKD-like phenotypes who underwent genetic testing that revealed pLoF IFT140-variants.

Findings: The 75 individuals (median age 56 years, 53.3% females) were from 61 families and were found to have 41 different monoallelic pLoF IFT140-variants. The majority of individuals presented with large, exophytic kidney cysts (median [range] total kidney volume 688 ml [201-4139]), and 90.2% were classified using the Mayo Imaging Classification as Mayo Class 2A. Arterial hypertension was present in 50.7% of the individuals (median [range] age at diagnosis 59 years [29-73]). Only one patient developed kidney failure (at age 69 years). A significant difference in age-adjusted eGFR between male and female patients was observed (P<0.001). 56.3% of the individuals over the age of 60 years had an eGFR less than 60ml/min/1.73m². The estimated genetic prevalence of monoallelic pLoF IFT140 variants was 19.76 (95%CI=18.8-20.7) and 27.89 (95%CI=23.8-31.9) per 10,000 in the Genome Aggregation Database and the 100,000 Genomes Project (100kG), respectively. CyKD (ICD-10 Q61) was associated with pLoF IFT140 variants (P=2.9x10^-9, OR=5.6 (3.3-9.2)) only in 100kG.

Study limitations: Retrospective study; younger patients and patients with milder forms of IFT140-related CyKD may not be diagnosed.

Conclusions: Individuals with monoallelic IFT140 pLoF variants are likely to develop kidney cysts atypical of classical ADPKD and generally have a favorable kidney prognosis.

Living-donor kidney transplant (LDKT) is the treatment of choice for patients with advanced kidney disease. Kidney paired donation (KPD), originally proposed to overcome immunological barriers, has now evolved to address biological and chronological incompatibilities and reduce financial disincentives. This strategy has allowed the maximization of the number of LDKTs. In 2021, of the 5,971 LDKTs performed, 1,115 (18.6%) were facilitated by KPD. Although KPD programs vary in size and structure, privately owned KPD programs dominate the landscape. Participation in KPD is far from universal: it is not offered in 40% of transplant centers. Across the United States, there are large areas devoid of transplant centers that offer KPD. As a result, some donor and recipient candidates are missing opportunities for a successful LDKT. Some private KPD programs provide financial and legal protections to living donors. Therefore, access to such donor protections is variable and not available to all donors. In this perspective, we review the evolution of KPD programs, explore ways to enhance participation, discuss the need for transparency about living donation options to donor and recipient candidates, and ultimately call for national action for regulatory oversight and to make living kidney donation financially neutral regardless of participation in KPD.

Proteinuria plays a central role in the diagnosis of kidney disease and has a high prognostic value. The test methods used differ considerably regarding impact on test accuracy, sensitivity, and specificity. Therefore, knowledge of the methodology is crucial for the interpretation of the results. In addition to the distinction between semi-quantitative and quantitative tests, there are also relevant differences within the two methods. In general, semi-quantitative tests are easy to handle but have limitations such as: i) incomplete quantification, ii) a lack of specificity regarding the type of proteinuria, iii) a high rate of false positive tests with the need for re-testing with a quantitative method for verification. In contrast, quantitative methods, especially immunoassays, have the advantages of: i) high test accuracy, ii) the possibility of targeted detection of specific protein molecules in addition to albumin. However, these methods are more expensive and require access to a laboratory or an electronic point of care device. In this review, the different types of tests for proteinuria, their underlying methodologies and their strengths and weaknesses are discussed in detail to allow a rational decision of use and a correct interpretation of the results depending on the clinical context.

Rationale & objective: Recipients of kidney allografts are at risk of osteoporotic fractures (OF), but the association of OF with transplant patient outcomes remains uncertain due to common coexisting risks and complex medical conditions. This study sought to assess whether the overall incidences of OF among recipients of kidney allografts compared to that of patients receiving maintenance dialysis for kidney failure.

Study design: A national retrospective cohort study.

Setting & participants: 145,090 Korean patients newly diagnosed with kidney failure between 2009 and 2019.

Exposure: Kidney transplantation versus dialysis resulting in OF, and OF increasing risk of death.

Outcome: Incident OF overall and by site (hip, spine, forearm, and humerus); death.

Analytical approach: Comparison of patients receiving maintenance dialysis with recipients of kidney allografts matched by age, sex, year of new index date, duration of dialysis, and presence of hypertension and diabetes mellitus. Cause-specific Cox proportional hazards regression models estimated the association between modality of kidney replacement therapy and OF. Cox models incorporating OF as a time-updated covariate were used to estimate the association of OF and mortality.

Results: A total of 11,413 pairs were matched. Over the entire study period, 541 (4.7%) OFs in allograft recipients and 657 (5.8%) in matched dialysis comparators occurred, respectively. After 5.5 years of follow-up evaluation, the risk of incident OF was lower in kidney transplant recipients compared with matched dialysis comparators (adjusted hazard ratio[AHR], 0.73 [95% CI, 0.64-0.84], P<0.001). The differences in fracture rates were primarily driven by differences in hip fractures. Incident OF was associated with increased mortality risk (AHR, 2.18 [95% CI, 1.57-3.02], P<0.001) and death-censored allograft failure (AHR, 1.42 [95% CI, 1.02-1.97], P=0.040).

Limitations: Use of claims data, and no data on bone mineral density or hyperparathyroidism; the definition of OF that was used encompassed traumatic fractures.

Conclusions: Kidney allograft recipients have a lower rate of incident OF compared with dialysis patients, but when OF occurs it is associated with a higher rate of death and allograft loss.