Podocyte-Parietal Epithelial Cell Interdependence in Glomerular Development and Disease
PECs are thought to contribute to disease progression and severity, and the interdependence between these two cell-types during development and in various manifestations of kidney pathology is the primary focus of this review.
KEY FINDINGS: PECs are thought to contribute to disease progression and severity, and the interdependence between these two cell-types during development and in various manifestations of kidney pathology is the primary focus of this review.
BACKGROUND: Podocytes and parietal epithelial cells (PECs) are among the few principal cell types within the kidney glomerulus, the former serving as a crucial constituent of the kidney filtration barrier and the latter representing a supporting epithelial layer that adorns the inner wall of Bowman's capsule.
DETAILS: Podocytes and PECs share a circumscript developmental lineage that only begins to diverge during the S-shaped body stage of nephron formation - occurring immediately before the emergence of the fully mature nephron. These two cell-types therefore share a highly conserved gene expression program, evidenced by recently discovered intermediate cell types occupying a distinct spatio-temporal gene expression zone between podocytes and PECs. In addition to their homeostatic functions, podocytes and PECs also have roles in kidney pathogenesis. Rapid podocyte loss in diseases such as Rapidly Progressive Glomerulonephritis (RPGN) and collapsing and cellular subtypes of Focal Segmental Glomerulosclerosis (FSGS) is closely allied with PEC proliferation and migration towards the capillary tuft - resulting in the formation of crescents and pseudo-crescents.
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Source: Bronstein, R., Pace, J., Gowthaman, Y., et al. (2023). Podocyte-Parietal Epithelial Cell Interdependence in Glomerular Development and Disease. Journal of the American Society of Nephrology . 2023; 10.1681/ASN.104. Published: February 16, 2023. DOI: 10.1681/ASN.0000000000000104.
Fracture Risk Remains High and Largely Unaddressed After Kidney Transplantation
Kidney transplant recipients had a 21% 10-year fracture risk, unchanged over two decades. Twenty-eight percent of those with a fracture sustained another fracture, with the highest incidence at 6-12 months. Only 10% received anti-osteoporosis therapy and 17% underwent DXA within 1 year, highlighting an unmet need for post-fracture risk assessment and intervention.
KEY FINDINGS: Kidney transplant recipients continue to experience substantial fracture risk, with approximately one in five developing a fracture within 10 years after transplantation. Fracture rates remained largely unchanged over two decades, and an initial fracture was followed by a particularly high risk of another fracture. The limited use of anti-osteoporosis therapy and DXA assessment after fracture highlights an important gap in post-transplant bone health management.
BACKGROUND: Kidney transplant recipients remain at increased risk of fractures compared with the general population. However, the magnitude of this risk in the current transplant era and the likelihood of subsequent fractures after an initial event have not been fully characterized. This study evaluated post-transplant fracture risk and prognosis over two decades.
DETAILS: This retrospective cohort study included all adults who underwent a first single-organ kidney transplant between 2000 and 2022 in Denmark. Nationwide health registries provided demographic, diagnostic, procedural, prescription, transplantation, and mortality data. The study assessed cumulative incidence of first and subsequent fractures, with death treated as a competing risk, and examined fracture incidence across different transplant periods.
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The cohort comprised 3977 kidney transplant recipients, with a median age of 50 (40, 60) years; 1487 (37%) were female. Before transplantation, 503 (13%) had a history of any fracture and 176 (4%) had experienced a major osteoporotic fracture.
Among 3977 kidney transplant recipients, 788 experienced a post-transplant fracture. The 10-year risk of any fracture was 21% (95% confidence interval 20–23). Crude fracture incidence remained unchanged across the study period from 2000 to 2022, although age- and sex-standardized estimates showed a slight decline. Fractures occurred predominantly at peripheral skeletal sites.
Twenty-eight percent of patients who sustained a fracture experienced a subsequent fracture, with the greatest incidence occurring 6–12 months after the initial event. The 2-year cumulative incidence of any subsequent fracture was 13% (95% CI 11–16), increasing to 24% (95% CI 21–28) at 5 years.
Despite the fracture burden, only 10% of patients received anti-osteoporosis therapy within 1 year after a fracture, and 17% underwent dual-energy X-ray absorptiometry (DXA) within 1 year.
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Source: Ystrøm, I. K., Christiansen, C. F., Ivarsen, P., et al. Fracture Risk After Kidney Transplantation: Unchanged and Unaddressed: A Registry-Based Cohort Study Across Two Decades. Clinical Kidney Journa. 2026; 19(3): sfag029. Published: March, 2026. DOI: 10.1093/ckj/sfag029.
Potassium Binders May Support Continued RAAS Inhibitor Therapy in Chronic Kidney Disease and Heart Failure
Second-generation potassium binders were associated with greater persistence of RASi and MRA therapy than first-generation binders. Continued RASi use was associated with lower observed mortality and hospitalization, but not with a clear difference in 3P-MACE. These findings suggest potassium binders may facilitate sustained RAASi therapy in CKD and HF.
KEY FINDINGS: In this Swedish nationwide observational cohort, second-generation potassium binders were associated with greater persistence of RASi and MRA therapy at 6 months than first-generation binders. RASi persistence was also associated with lower observed all-cause mortality and hospitalization, although no clear difference in 3P-MACE was identified. The findings support the potential role of potassium binders in maintaining guideline-directed RAASi therapy in patients with CKD and/or HF.
BACKGROUND: Renin–angiotensin–aldosterone system inhibitors (RAASi) provide important cardiorenal benefits in chronic kidney disease (CKD) and heart failure (HF), but their use can increase the risk of hyperkalemia. Hyperkalemia frequently leads to RAASi discontinuation despite the benefits of continued therapy. This study evaluated whether potassium binders, particularly second-generation agents, were associated with greater persistence of RAASi and mineralocorticoid receptor antagonist (MRA) therapy.
DETAILS:
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Source: Furuland, H., Larsson, A. O., Uhde, M., et al. Potassium Binders and Continuation of Renin–Angiotensin System Inhibitors/Mineralocorticoid Receptor Antagonist in Chronic Kidney Disease and Heart Failure (the DEMONSTRATE Database. Journal of Internal Medicine. 2026; 300(2): 179-192. Published: Augusts, 2026. DOI: 10.1111/joim.70087.
Hyponatremia Treatment Guidelines: Maintain Cautious Correction to Prevent Osmotic Demyelination
Current hyponatremia correction safeguards should be maintained. For chronic hyponatremia with sodium 120 mmol/L or lower, correction should generally remain within 10-12 mmol/L in 24 hours and 18 mmol/L in 48 hours; high-risk patients require a stricter limit of 8 mmol/L in 24 hours. Frequent monitoring and desmopressin may prevent overcorrection.
KEY FINDINGS: Current safeguards for severe hyponatremia remain warranted despite recent evidence questioning restrictive correction limits. Correction should be particularly cautious in patients with sodium ≤105 mmol/L or other ODS risk factors. Frequent serum sodium measurement and urine-output monitoring are essential because spontaneous water diuresis can cause rapid sodium increases. Desmopressin may help prevent or reverse excessive correction.
BACKGROUND: Severe hyponatremia can cause life-threatening neurologic complications, while overly rapid correction can result in osmotic demyelination syndrome (ODS). Recent retrospective evidence has questioned whether existing correction limits are overly restrictive. This review reassesses the evidence supporting current treatment safeguards and emphasizes continued caution when correcting severe hyponatremia.
DETAILS: The review examines the evidence underlying international recommendations for limiting the rate of serum sodium correction, with particular attention to patients with severe or chronic hyponatremia. The authors discuss evidence linking rapid correction with ODS and review data that have challenged the need for conservative correction limits.
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For chronically hyponatremic patients with serum sodium ≤120 mmol/L who are at normal risk for ODS, the US/Irish expert panel recommends limiting correction to 10–12 mmol/L during any 24-hour period and 18 mmol/L during any 48-hour period, with a minimum correction of 4–8 mmol/L. Patients at increased risk of ODS—including those with sodium ≤105 mmol/L, alcohol use disorder, hypokalemia, malnutrition, or advanced liver disease—should have correction limited to 8 mmol/L in any 24-hour period, with a minimum daily correction goal of 4–6 mmol/L.
For patients with severe symptoms, European and US/Irish recommendations support bolus administration of hypertonic saline to increase serum sodium by approximately 5 mmol/L or 4–6 mmol/L, respectively, within a few hours. The review notes that this initial increase can substantially reduce intracranial pressure and may reverse impending brain herniation.
The review concludes that current safeguards for treating severe hyponatremia should not be abandoned. Excessive increases in serum sodium can occur because of sudden elimination of dilute urine rather than excessive saline administration. Water diuresis may increase serum sodium by more than 2 mmol/L per hour, emphasizing the need for frequent serum sodium measurements and close monitoring of urine output in patients with sodium ≤120 mmol/L.
Desmopressin can be used to prevent or reverse inadvertent overcorrection. A strategy involving scheduled desmopressin with controlled hypertonic saline administration, termed the "DDAVP clamp"", has been reported to help achieve correction targets, although comparative evidence remains limited.
The review highlights that patients with sodium ≤105 mmol/L and additional risk factors for ODS are particularly vulnerable. If correction exceeds 8 mmol/L in less than 24 hours in these high-risk patients, relowering the serum sodium should be considered.
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Source: Sterns, R. H., Rondon-Berrios, H., Adrogué, H. J., et al. Treatment Guidelines for Hyponatremia: Stay the Course. Clinical Journal of the American Society of Nephrology. 2026; 19(1): 129-135. Published: January, 2024. DOI: 10.2215/CJN.0000000000000244.
High-Quality Donor Kidneys Frequently Allocated to Adults Despite Pediatric Priority
Among deceased-donor kidneys with KDPI-10 below 35%, 23.4% were allocated to higher-priority adults. For ideal pediatric-quality kidneys, this proportion was 34.3%, with 77.5% received by multiorgan transplant recipients. KDPI-8 is unlikely to materially change pediatric access to ideal donor kidneys.
KEY FINDINGS: Despite pediatric allocation priority, a substantial proportion of high-quality donor kidneys continues to be allocated to adults with greater priority, predominantly multiorgan transplant recipients. The revised KDPI-8 calculation is not expected to materially alter the proportion of ideal pediatric-quality kidneys prioritized for children, although it changes the clinical composition of the donor pool by increasing the proportion of HCV-seropositive donors and reducing the proportion of donors after circulatory death. These findings highlight persistent limitations of KDPI-based allocation for pediatric candidates and support continued evaluation of policies that balance equity, donor-recipient matching, and long-term transplant outcomes.
BACKGROUND: Children receive allocation priority for deceased-donor kidneys with a kidney donor profile index (KDPI) <35%, although certain adult candidates retain higher priority. The recent transition from the 10-variable KDPI (KDPI-10) to the revised 8-variable KDPI (KDPI-8), which excludes donor race and hepatitis C virus (HCV) status, raised questions regarding its potential effect on pediatric access to high-quality donor kidneys.
DETAILS: This retrospective cohort study analyzed 60,587 deceased donors and their kidney recipients recorded in the Organ Procurement and Transplantation Network registry from January 1, 2018, through December 31, 2023. The investigators compared donor characteristics and kidney allocation patterns using KDPI-10 and KDPI-8. Ideal pediatric-quality donors were defined as donors with a KDPI <35%, donation after brain death, age <35 years, creatinine <=1.5 mg/dL, and no infectious risk, diabetes, or hypertension. Among kidneys from donors with KDPI-10 <35%, 23.4% were allocated to adults in categories with greater priority than pediatric candidates. Among ideal pediatric-quality kidneys, 34.3% were allocated to these higher-priority adult recipients, and 77.5% of these transplants were received by multiorgan transplant recipients. The proportion of donors meeting ideal pediatric-quality criteria was similar with KDPI-10 and KDPI-8 calculations (32.7% vs 33.5%). However, the KDPI-8 group included more Black donors (15.3% vs 9.9%) and HCV-seropositive donors (11.1% vs 3.6%) and fewer donors after circulatory death (12.7% vs 20.3%).
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Source: Sonnenberg, E. M., Amaral, S., Zhang, S., et al. Allocation of Kidney Allografts From Donors With Kidney Donor Profile Index <35% and the Impact of Kidney Donor Profile Index Revisions on Access to Transplantation for Children. American Journal of Kidney Diseases. 2026; Published: August 22, 2026. DOI: 10.1053/j.ajkd.2026.02.643.
Nationwide Recall of Cetirizine Hydrochloride Tablets USP 5 mg Due to Potential Ranitidine Cross-Contamination
Four nationwide-distributed lots of Cetirizine Hydrochloride Tablets USP 5 mg are being voluntarily recalled because of potential ranitidine cross-contamination. Patients with ranitidine hypersensitivity may be at risk for severe allergic reactions or anaphylaxis. No recall-related adverse events had been reported.
KEY FINDINGS: Unique Pharmaceutical Laboratories has initiated a voluntary nationwide recall of four lots of Cetirizine Hydrochloride Tablets USP 5 mg because of potential cross-contamination with ranitidine. The affected product was distributed nationwide in 100-count HDPE bottles under the Rising Pharma Holdings Inc. brand. Patients with hypersensitivity to ranitidine ingredients may be at risk for serious reactions, including severe hypersensitivity and life-threatening anaphylaxis. No adverse events related to the recalled product had been reported at the time of the announcement.
The recall was initiated after a pharmacy technician identified a discrepancy while counting tablets during dispensing. A product complaint described red dots and discoloration on some cetirizine tablets. The recalled lots are GY825029, GY825030, GY825031, and GY825032, each with an expiration date of 10/2028 and NDC 16571-401-10.
The manufacturer and distributor are arranging the return of the affected products. Clinicians should consider the recall when evaluating patients who may have received the affected medication and should assess and manage any suspected adverse reactions appropriately.
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Source: Unique Pharmaceutical Laboratories (A Div. of J. B. Chemicals & Pharmaceuticals Ltd.) Issues Voluntary Nationwide Recall of Cetirizine Hydrochloride Tablets USP 5 mg Due to Potential Cross Contamination with Ranitidine. FDA. Published: July 20, 2026.
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