Background/Objectives: Diet is a modifiable determinant of kidney health, and sex differences in kidney physiology support sex-specific evaluation of dietary patterns. We examined the association of Planetary Health Diet Index (PHDI) adherence with cystatin C-based eGFR decline, and its modification by sex, in US adults aged 50 years and older. Methods: We analyzed 2126 Health and Retirement Study participants (950 men, 1176 women) with diet assessed by food frequency questionnaire in 2013 and cystatin C-based eGFR measured in 2012 and 2016. Survey-weighted regression models, adjusted for baseline eGFR and for demographic, socioeconomic, lifestyle and clinical covariates, related PHDI to eGFR change and to a ≥30% relative eGFR decline; sex interaction was tested on the multiplicative and additive scales. Results: PHDI adherence was nonsignificantly associated with lower eGFR decline (β per 10-point increment 0.218; 95% CI −0.065 to 0.466). Among women, each 10-point-higher score was associated with slower eGFR decline (β 0.355; 95% CI 0.029 to 0.681; p = 0.034) and 20% lower odds of ≥30% eGFR decline (OR 0.799; 95% CI 0.687 to 0.930; p = 0.005); no significant association was observed in men (β 0.080; 95% CI −0.294 to 0.454; OR 1.080; 95% CI 0.901 to 1.295). Sex modified the association with ≥30% eGFR decline on both a multiplicative (p = 0.002) and additive scale (p < 0.001). Conclusions: PHDI adherence was associated with slower kidney function decline in women aged 50 years and older, with non-significant effect in men. Sex merits consideration as a biological modifier when plant-forward diets are evaluated as potentially nephroprotective strategies.

Heart failure affects more than 64 million people worldwide, and admissions for acute decompensation account for a substantial proportion of cardiovascular healthcare expenditure. Achieving complete decongestion remains the principal objective of inpatient management, yet many patients are discharged with persistent volume overload, a consistent predictor of early rehospitalization and mortality. Loop diuretics have remained the cornerstone of decongestive therapy for more than six decades; however, their effectiveness is frequently limited by diuretic resistance, leaving many patients incompletely decongested despite dose escalation. Diuretic resistance reflects adaptive sodium retention distributed across multiple nephron segments, a process that extends well beyond the loop itself. Distal-tubular-remodeling-enhanced proximal sodium reabsorption, neurohormonal activation, post-diuretic sodium retention, and impaired tubular drug delivery collectively blunt natriuretic responsiveness, explaining why progressive loop–dose escalation often yields diminishing returns. Sequential nephron blockade provides a physiology-based strategy that matches the adjunct agent to the predominant mechanism of sodium retention. We integrate contemporary randomized evidence with renal tubular physiology to propose a mechanism-based approach: acetazolamide for patients with hypochloremic metabolic alkalosis and enhanced proximal sodium reabsorption, thiazide-type diuretics when distal cotransporter escape predominates, vasopressin antagonists for dilutional hyponatremia complicating congestion, and sodium–glucose cotransporter 2 inhibitors as foundational therapy that combines modest acute natriuresis with durable cardiorenal protection. Early assessment of natriuretic response using spot urine sodium further enables individualized treatment escalation. Together, these concepts move sequential nephron blockade beyond empirical combination diuretic therapy toward a mechanism-based strategy for overcoming diuretic resistance. We propose a personalized, phenotype-driven framework in which early urinary sodium response, kidney function, serum chloride, acid–base status, serum sodium, background SGLT2 inhibitor therapy, and venous congestion imaging guide the selection, escalation, and de-escalation of adjunctive therapy, with the goal of more complete and safer decongestion in acute decompensated heart failure. Matching adjunct choice to a patient’s individual biochemical phenotype, rather than applying diuretics in a fixed sequence, exemplifies precision medicine applied to acute decongestive therapy.

Renal impairment affects up to half of patients with newly diagnosed multiple myeloma, and roughly 2–4% require dialysis at presentation, most often because of light-chain cast nephropathy. In these patients, renal recovery is associated with the speed and magnitude of serum free light-chain (sFLC) reduction in observational cohorts, an association that mainly reflects the hematologic response to chemotherapy; the incremental benefit of removing circulating sFLCs by extracorporeal means remains uncertain, and this narrative review is organized around that question in the current era of effective antimyeloma therapy. Plasma exchange was tested in three small randomized trials before proteasome inhibitors were available, the largest finding no benefit, and two randomized trials of high-cutoff hemodialysis on a bortezomib backbone, MYRE and EuLITE, found no benefit for their primary renal endpoints, with more pulmonary infections in the high-cutoff arm of EuLITE. Medium-cutoff membranes, polymethylmethacrylate adsorptive dialyzers, and hemodiafiltration with endogenous reinfusion have achieved substantial sFLC reduction with less albumin loss in small uncontrolled series, without any randomized comparison against conventional dialysis. Daratumumab-containing induction lowers sFLCs within days and may further narrow the residual rationale for enhanced clearance. Conventional high-flux hemodialysis combined with prompt antimyeloma therapy is therefore the evidence-based standard kidney-replacement modality when dialysis is indicated; the patient subsets in which a time-limited enhanced-removal strategy might still be tested are proposed as hypotheses for prospective trials, without validated thresholds.

Cardiorenal syndrome describes the clinical consequences of the bidirectional influence that cardiac and renal dysfunction exert on each other—a domain in which single-organ care proves insufficient. A 2024 meta-analysis estimated the pooled prevalence of chronic kidney disease among patients with heart failure at 49%. Across individual cohorts, this figure ranges between 30% and 60%, with the spread reflecting the population studied and the threshold used to define kidney disease. Among acute heart failure admissions, 64% of cases have an estimated glomerular filtration rate below 60 mL/min/1.73 m², and mortality reaches 7.6% once it falls into the severe range (15–29 mL/min/1.73 m²). The same can be described in the other “direction”: congestive heart failure is reported in 28% of adults aged 66 years or older with chronic kidney disease, compared to 6% of those without. The Acute Dialysis Quality Initiative distinguishes a five-subtype framework by direction and chronicity of organ injury, and each subtype shows characteristic prescribing failure patterns. In types 1 and 2, the dominant problem is premature de-escalation of neurohormonal therapy at the first creatinine rise. In type 4, the failure is upstream in the cascade: cardiovascular surveillance lags behind the increasing rate of chronic kidney disease. Randomized trials over the past decade have expanded the therapeutic options. Sodium-glucose cotransporter 2 inhibitors showed cardiorenal benefit across every ejection fraction studied and at estimated glomerular filtration rate values down to 20 mL/min/1.73 m². These findings have expanded treatment eligibility to patients with advanced CKD. The FINE-HEART pooled analysis of finerenone suggested a nominal reduction in all-cause mortality, alongside fewer heart failure hospitalizations and improvement in the kidney composite outcome. In the FLOW trial, semaglutide showed a reduction in the composite of major kidney events and cardiovascular death in diabetic adults with chronic kidney disease. In this cohort, the estimated glomerular filtration rate slope was slower in the active arm and secondary outcomes showed reductions in major adverse cardiovascular events and in all-cause mortality. However, observational registries show that these classes of drugs are less used in patients with the highest baseline risk, with advancing renal disease identified as an independent predictor of under-prescription. Therapeutic inertia in this setting reflects determinants at the patient, clinician, and system levels, which is compounded because each prescribing decision must be justified for both the heart and the kidney. The primary objective of the present narrative review is the therapeutic inertia that separates this evidence from routine prescribing: the sections on pathophysiology, imaging and biomarker tools, and subtype-specific pharmacotherapy supply the clinical rationale, and the closing sections cover the implementation strategies and the multidisciplinary framework required to act on the trial findings.