Background: Although renal replacement therapy prevents death from uremia, survival among patients with acute and chronic kidney diseases (CKD) remains an imperative concern. The expected life span of US dialysis patients 60–64 years of age is approximately 4.5 years; this is similar to that of patients with lung cancer. Despite substantial progress in many medical specialties over the past decades (e.g., notable reductions in myocardial infarction, stroke, and mortality rates in the general population), survival among dialysis patients has not improved significantly over the same period. A few decades ago, HIV infection and AIDS were pretty much a death sentence. Because of progress in HIV treatment, now it can be controlled with a daily pill, and ongoing research is pushing treatment even further and controls the virus with longer-acting treatment. A cure is no longer impossible for HIV and other viral infections such as hepatitis B and C and many malignancies, but so far there is no cure for CKD. Summary: Billions of dollars have been spent on kidney disease research in the past decades, with no tangible progress in clinical practice. The challenges of improving the quantity and quality of trials in nephrology are enormous. The number of randomized controlled trials (RCTs) published in nephrology is lower than that in other medical subspecialties, and most of the big RCTs in nephrology yield negative results. Nephrology studies evaluating hard clinical endpoints or surrogate endpoints are scarce. Key Message: Herein we discuss the slow progress in nephrology research that has impacted clinical practice over the last couple of decades and highlight the major obstacles, challenges, and potential solutions.
Background The aim of this retrospective analysis was to investigate the effect of human leukocyte antigen (HLA) and calculated panel reactive antibody (cPRA) on BK virus activation as evidenced by BK viremia (BKV). Patients and Methods At our institution, 649 kidney transplant patients were screened for BKV from 2009 to 2017. Patients were considered to have BKV if they had >10 000 copies/mL of BK DNA in their blood. Donor and recipient HLA and cPRA, demographic, clinical and laboratory data, as well as immunosuppressive medications were collected. Results We identified 122 BK positive and 527 BK negative patients. Only 25% of the patients had cPRA of 20% or more, and 64% had more than three HLA‐A, ‐B, and ‐DR mismatches. In both univariate and multivariate analyses, male gender, age, and maintenance of steroid therapy significantly increased the risk of BKV (P = 0.005, 0.005 and <0.001, respectively). The degree of cPRA and the individual HLA allele and HLA allele matching did not significantly affect BKV. Conclusion Neither the degree of HLA mismatching nor cPRA appears to affect BKV. Moreover, no specific HLA allele, HLA allele matching, or cPRA were associated with BKV.
Parathyroid hormone (PTH) 1-84 is the main biologically active hormone produced by the parathyroid cells. Circulating PTH molecules include the whole PTH 1-84 along with amino (N) and carboxyl (C) terminal fragments. While PTH is the best available noninvasive biomarker to assess bone turnover in dialysis patients, the biological roles of individual circulating PTH fragments are still not completely known. The understanding that there is an enormous variation in the target specificity of currently available PTH assays for different circulating forms of PTH has led to the evolution of assays from first to second then third generation. With a reduction in kidney function, there is a preferential increase in circulating C fragments and non-PTH 1-84 forms, resulting in a decrease in the ratio of PTH 1-84/non-PTH 1-84. However, there are also substantial differences in between-assay measurements, with several fold variations in results. Targets based on multiples of the upper limit of normal (ULN) should be used rather than PTH ranges using absolute iPTH values. To date, the second-generation PTH remains the most widely used assay. Current guidelines recommend following iPTH trends rather than absolute values. Herein, we highlight problems and challenges in PTH assays/measurements and their interpretations in dialysis patients.
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