Kidney360最新文献

Background: 3D imaging and histology are critical tools for assessing polycystic kidney disease ( PKD ) in patients and animal models. Magnetic resonance ( MR ) imaging provides micron resolution, but is time consuming, expensive, and access to equipment and expertise is limiting. Robotic ultrasound ( US ) imaging has lower spatial resolution but is faster, more cost effective, and accessible. Similarly, Picrosirius red ( PSR ) staining and brightfield microscopy is commonly used to assess fibrosis; however, alternative methods have been shown in non-kidney tissues to provide greater sensitivity and more detailed structural characterization.

Methods: In this study, we evaluated the utility of robotic US and alternative methods of quantifying PSR staining for PKD research. We compared longitudinal total kidney volume ( TKV ) measurements using US and MR. We additionally compared PSR imaging and quantification using standard brightfield with that by circularly polarized light with hue analysis, and fluorescence imaging analyzed using CT-FIRE software for automatic detection of individual collagen fibers.

Results: Increased TKV was detected by US in Pkd1RC/RC vs wild type ( WT ) at timepoints spanning early to established disease. US inter-observer variability was greater but allowed scanning in 2-5 minutes/mouse while MR required 20-30 minutes/mouse. While no change in fibrotic index was detected in this cohort of relatively mild disease using brightfield, polarized light showed fibers skewed thinner in Pkd1RC/RC vs WT. Fluorescence imaging showed a higher density of collagen fibers in Pkd1RC/RC vs WT, and fibers were thinner and curvier with no change in length. Additionally, fiber density was higher in both glomeruli and tubules in Pkd1RC/RC , and glomeruli had a higher fiber density than tubules in Pkd1RC/RC , and trended higher in WT.

Conclusions: These studies show robotic ultrasound is a rigorous imaging tool for pre-clinical PKD research. Additionally, they demonstrate the increased sensitivity of polarized and fluorescence analysis of PSR-stained collagen.

Background: Hyponatremia treatment guidelines recommend avoiding excessive increases in serum sodium concentration (s[Na]) to prevent osmotic demyelination syndrome. Although an unexpected rise in s[Na] has been attributed to water diuresis during the treatment of hyponatremia, clinical courses of water diuresis are unclear. We conducted this study to investigate the clinical characteristics of water diuresis during profound hyponatremia management.

Methods: In this retrospective observational study, we examined patients with profound hyponatremia (s[Na] ≤120 mEq/L) admitted to the intensive care unit of a Japanese hospital. The manifestation of water diuresis was defined as a urine volume ≥2 ml/kg/h and a urinary sodium plus potassium concentration (u[Na+K]) ≤50 mEq/L. We analyzed changes in urine volume and u[Na+K] over time for patients experiencing water diuresis. This analysis employed a mixed-effects model with spline terms for time, and the results are graphically presented.

Results: Among 47 eligible patients, 30 (64%) met the criteria for water diuresis. The etiologies of hyponatremia were drug-related hyponatremia (n=10; 33%), primary polydipsia (n=8; 27%), hypovolemic hyponatremia (n=7; 23%), syndrome of inappropriate secretion of antidiuresis (n=7; 23%), and acute heart failure (n=1; 3%). Among patients with water diuresis, 27 (90%) experienced the manifestation of water diuresis within 24 hours after the start of correction. The increased urine volume and decreased u[Na+K] levels began several hours before the peak manifestation of water diuresis. Within 6 hours after the manifestation of water diuresis, 29 patients (97%) received electrolyte-free infusions and 14 (47%) received desmopressin. One patient (3%) with water diuresis experienced overcorrection.

Conclusions: Water diuresis is common during the treatment for profound hyponatremia and typically occurs within the first 24 hours, preceded by changes in urinary characteristics. Early detection and prompt response to water diuresis through urine monitoring during the early periods of hyponatremia treatment may be effective for managing water diuresis.

The sodium chloride co-transporter (NCC) fine-tunes Na+ balance and indirectly affects the homeostasis of other ions including K+, Mg2+ and Ca2+. Due to its effects on Na+ balance, blood pressure is significantly affected by alterations in NCC activity. Several factors have been reported to influence the expression and activity of NCC. One critical factor is NCC phosphorylation/dephosphorylation that occurs at key serine-threonine amino acid residues of the protein. Phosphorylation, which results in increased NCC activity, is mediated by the WNK-SPAK/OSR1 kinases. NCC activation stimulates reabsorption of Na+, increasing extracellular fluid volume and hence blood pressure. On the other hand, proteasomal degradation of WNK kinases following ubiquitination by the CUL3-KLHL3 E3 ubiquitin ligase complex and dephosphorylation pathways oppose WNK-SPAK/OSR1-mediated NCC activation. Components of the CUL3/KLHL3-WNK-SPAK/OSR1 regulatory pathway may be targets for novel anti-hypertensive drugs. In this review, we outline the impact of these regulators on the activity of NCC and the consequent effect on blood pressure.

Lupus nephritis (LN) is the most common major organ manifestation of the autoimmune disease systemic lupus erythematosus (SLE, lupus), with 10% of those afflicted progressing to end-stage kidney disease. The kidney in LN is characterized by a significant immune infiltrate and proinflammatory cytokine milieu that affects intrinsic renal cells and is, in part, responsible for the tissue damage observed in LN. It is now increasingly appreciated that LN is not due to unidirectional immune cell activation with subsequent kidney damage. Rather, the kidney microenvironment influences the recruitment, survival, differentiation and activation of immune cells, which in turn modify kidney cell function. This review covers how the biochemical environment of the kidney (i.e. low oxygen tension and hypertonicity) and unique kidney cell types affect the intrarenal immune cells in LN. The pathways employed by intrinsic renal cells to interact with immune cells, such as antigen presentation and cytokine production, are discussed in detail. An understanding of these mechanisms can lead to the design of more kidney-targeted treatments and the avoidance of systemic immunosuppressive effects and may represent the next frontier of LN therapies.

Background: Hyperkalemia is a known complication of chronic kidney disease (CKD); however, it is not known whether hyperkalemia directly contributes to CKD progression and the risk of death. Clarifying the extent to which hyperkalemia is associated with CKD progression and mortality can inform clinical practice and guide future research. The objective of this study was to quantify the risks of CKD progression and mortality associated with hyperkalemia in patients with stages 3b/4 CKD.

Methods: This was a real-world, exact and propensity score-matched, observational cohort study using data (January 2016-December 2021) from Optum's deidentified Market Clarity Data, a large US integrated insurance claims/electronic medical record database. The study included matched adult patients with stages 3b/4 CKD with and without hyperkalemia, not regularly treated with an intestinal potassium (K+) binder. Measured outcomes were CKD progression and all-cause mortality. CKD progression was defined as diagnosis of CKD stage 4 (if stage 3b at index), CKD stage 5 or kidney failure, or receipt of dialysis or kidney transplantation.

Results: After matching, there were 6,619 patients in each of the hyperkalemia and non-hyperkalemia cohorts, with a mean (standard deviation) follow-up time of 2.12 (1.42) years. Use of any renin-angiotensin-aldosterone system inhibitors (RAASi) during baseline was common (75.9%) and most patients had CKD stage 3b (71.2%). Patients with hyperkalemia had a 1.60-fold (95% confidence interval [CI] 1.50, 1.71) higher risk of CKD progression and a 1.09-fold (1.02, 1.16) higher risk of all-cause mortality relative to patients without hyperkalemia. Relative risks of CKD progression associated with hyperkalemia were similar within the subset of patients receiving RAASi and across CKD stages, and when alternative definitions of CKD progression were used.

Conclusions: Patients with CKD stages 3b/4 and hyperkalemia experienced significantly higher risks of CKD progression and all-cause mortality than propensity score-matched patients without hyperkalemia.

Kidneys play a crucial role in maintaining homeostasis within the body, and this function is intricately linked to the vascular structures within them. For vascular cells within the kidney to mature and perform their functions effectively, it is imperative that there is a meticulous and well-coordinated spatial alignment between the nephrons and the intricate network of blood vessels within the organ. This spatial arrangement ensures efficient filtration of blood and regulation of the electrolyte balance, blood pressure, and fluid levels. Additionally, the kidneys play a vital role in the regulation of acid-base balance and the production of hormones involved in erythropoiesis and blood pressure regulation. Thus, the close interaction between the vascular system and the kidney's structural organization is essential for maintaining overall physiological balance and health. This article focuses on the vascular development of the kidneys, summarizing the current understanding of the origin and formation of the renal vasculature, and the crucial molecules involved. By elucidating the cellular and molecular mechanisms governing renal vascular development, this article aims to promote advancements in renal regenerative medicine and provide potential avenues for therapeutic interventions to address kidney disease.

Background: Depression and diminished health-related quality of life (HRQOL) are common in kidney failure. In this study we investigate whether kidney transplant (KT), the treatment of choice for kidney failure, improves depression and HRQOL across lifespan and whether this effect is sustained.

Methods: In this longitudinal observational cohort study, we assessed depression and HRQOL in patients on the KT waitlist and again at 3-months and 1-year after KT. We measured depression using the Beck Depression Inventory-II (BDI-II) and HRQOL using the Kidney Disease Quality of Life Short Form Version 1.3 (KDQOL-SF) physical health composite score (PCS) and mental health composite score (MCS). We used linear mixed effect models with random intercepts for patients to evaluate the effect of time, age, and KT status on BDI-II score, PCS, and MCS. For models with significant age interactions, we estimated this effect for baseline age groups.

Results: We analyzed 239 longitudinal BDI-II assessments completed by 99 patients and 143 KDQOL-SF assessments completed by 59 patients (16% Black, 79% White). The BDI-II scores improved pre- to post-KT (10 pre-KT vs 5 post-KT, p<0.001). PCS improved pre- to post-KT in younger patients, but the magnitude of change was lower with older age (p for interaction=0.01). In the sub-group analysis by age, there was improvement in PCS post-KT in patients <60 years (p=0.003 for 30-39, p=0.007 for 40-49, p=0.03 for 50-59). The MCS also improved from 47 pre-KT to 51 post-KT (p<0.001), and the magnitude of improvement was again lower with older age (p for interaction=0.03).

Conclusions: Depression and HRQOL improve with KT. While depression improves in all ages, the improvement in HRQOL, especially PCS, is more evident in younger patients. This improvement in depression and HRQOL is sustained until at least 1-year post-KT. These data help frame expectations for patients and transplant teams.

Background: Brazil has the largest Public Health System providing universal coverage for chronic dialysis. The objective was to describe the number, sociodemographic, and clinical characteristics of patients undergoing kidney replacement therapy (KRT) by dialysis within the Public Health System in Brazil.

Methods: We carried out a retrospective cohort study analyzing the database from the Brazilian Public Health System, focusing on procedures related to KRT. The study encompassed both prevalent and incident patients who underwent KRT in Brazil between 2015 and 2023.

Results: We observed an increase in the number and prevalence rate of dialysis patients from 2015 to 2023. We also noticed an increase in the age at dialysis initiation and in the prevalence of mixed-race patients and a reduction in the proportion of those undergoing peritoneal dialysis and with arteriovenous fistula. We identified an upward trajectory in the values of single-pool Kt/V over the years, contrasting with a decline in hemoglobin levels. The overall estimated prevalence rate of dialysis patients increased from 654 per million population (pmp) to 792 pmp over the years. The survival rates of incident KRT patients at 12 and 96 months were 81% and 60%, respectively.

Conclusion: We reported an increase in the age at which dialysis began and a decline in the adoption of peritoneal dialysis over the years. While there have been some improvements over the years resulting in better adequacy of hemodialysis as measured by Kt/V, controlling certain parameters such as hemoglobin levels has remained challenging.