Faculty Bibliography

The role of genetic testing for kidney stone formers remains incompletely resolved. The purpose of this paper is to review the role of genetics in kidney stone disease and provide guidance on the utility of genetic testing to overall reduce the burden of the disease for our patients. Genetic testing is a send-out laboratory test for most medical centers in the United States. However, access to such testing has been easier with options for genetic kit delivery to health care offices and even conveniently to patients' homes. The rise of genetic testing in medicine has advanced the field of nephrology in general and kidney stones specifically. It is our aim to provide basic knowledge on the approach to kidney stone disease to physicians, especially nephrologists and nephrology fellows, while also considering the appropriateness of genetic testing.

Urolithiasis is increasingly common, with rising rates driven by obesity, diabetes and metabolic syndrome. Patients with cancer have additional, unique risks of stone formation owing to effects on fluid and electrolyte balance, systemic cancer therapies, tumour lysis syndrome and anatomical alterations after urinary diversion or nephrectomy. Moreover, urolithiasis itself has been linked to increased rates of renal cell carcinoma, urothelial carcinoma and bladder cancer, potentially mediated by chronic inflammation, recurrent infections and shared metabolic or environmental factors. Management in this setting is complex and must be individualized. Percutaneous nephrolithotomy achieves the highest stone-free rates in patients with altered urinary tract anatomy, whereas retrograde intrarenal surgery and shock wave lithotripsy have more selective roles. Preventive strategies focus on thorough metabolic evaluation, hydration optimization and addressing cancer-specific risk factors such as hypercalcaemia, acidosis and chronic urinary stasis. Despite these insights, data on the epidemiology, mechanistic underpinnings and optimal management of urolithiasis in patients with cancer remain limited. Prospective studies are needed to clarify causal relationships, refine preventive strategies and develop evidence-based treatment algorithms for this growing and complex population.

Ultrasound is the imaging study of choice for the initial diagnosis of autosomal dominant polycystic kidney disease (ADPKD) due to its high diagnostic accuracy and ability to detect kidney cysts as small as 2 to 3 mm. MRI of the kidneys is also highly sensitive at detecting small cysts and is an alternative to US. MRI is the preferred modality for determining total kidney volume (TKV). TKV can be used as an imaging biomarker to predict kidney function decline, track disease progression, and evaluate the effectiveness of treatment. CT abdomen and pelvis with contrast is the test of choice for detecting suspected complications such as renal cyst hemorrhage, rupture, or infection. MRI of the abdomen without and with contrast can also be used for diagnosing complications of ADPKD and is usually appropriate regardless of kidney function. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

BACKGROUND:Hypercalciuria is a prominent characteristic in Dent disease type 1 (DD1) and is associated with kidney stones and nephrocalcinosis. The objectives of this study were to assess fibroblast growth factor 23 (FGF23) and 24,25-dihydroxyvitamin D (24,25(OH)2D) in DD1 patients and investigate the effects of phosphate supplementation on urinary calcium excretion. METHODS:Serum and 24-hour urine assessments from adult and pediatric DD1 patients (n=10 adults; n=9 pediatrics) were compared to adult control subjects with a history of idiopathic calcium kidney stones and hypercalciuria (n=9). Adult DD1 patients and control participants completed an oral phosphate supplementation intervention (1g/day x 14 days) with reassessment immediately following intervention. RESULTS:FGF23 was significantly lower in DD1 than in the control cohort (adults, p=0.006) and positively correlated with 24,25(OH)2D across all study cohorts. The concentrations of 24,25(OH)2D were low with conversion ratios (25-hydroxyvitamin D:24,25(OH)2D) exceeding the clinical reference limit for five of 10 adults and six of nine pediatric DD1 patients. The DD1 cohorts were then stratified by the 24,25(OH)2D ratio into "normal" and "low" 24,25(OH)2D. Adult DD1 patients with low 24,25(OH)2D (n=5) had lower FGF23, higher 1,25(OH)2D, greater urine calcium, and greater urine protein. Pediatric stratified data mirrored that in adults with the exception of no difference in serum 1,25(OH)2D. Phosphate supplementation was effective in decreasing urine calcium in both adult DD1 and control adult cohorts. CONCLUSIONS:Clinical measurement of 24,25(OH)2D is a novel and useful analysis for evaluating the severity of calcium and protein dysregulation in DD1. In addition, moderate phosphate supplementation effectively mitigates urine calcium excretion in DD1 adult patients.

PURPOSE OF REVIEW/OBJECTIVE:Medullary sponge kidney (MSK) is a congenital disorder of the distal nephron, characterized by cystic dilatation of the papillary and medullary tubules. It commonly presents with recurrent calcium nephrolithiasis and often, severe, life-altering chronic pain syndromes, often independent of urinary obstruction and of uncertain etiology. Management focuses on stone prevention and symptomatic care, but these measures are frequently inadequate. No studies of management of this pain syndrome in these patients have been performed. There are essentially no studies evaluating renal denervation in MSK specifically, although the technique has been utilized with some benefit in other disorders, underscoring a major therapeutic gap. In this review, we describe patients with MSK and chronic pain syndrome and review the role of renal denervation as a potential therapy. RECENT FINDINGS/RESULTS:Renal denervation may represent a promising strategy for chronic kidney pain syndrome. It could provide pain relief and improve quality of life in affected patients. SUMMARY/CONCLUSIONS:The optimal management strategy for chronic pain in MSK has not been elucidated. Renal denervation has recently been utilized and approved for the management of blood pressure. It could be useful for managing chronic kidney pain in this condition as well.

PURPOSE OF REVIEW/OBJECTIVE:The 2023 CONVINCE trial demonstrated improved survival with high-dose hemodiafiltration (HDF), prompting discussions about widespread adoption. However, this clinical advancement occurs amid growing awareness of healthcare's environmental impact, particularly dialysis treatments that consume extensive water and energy resources. This review examines the environmental implications of HDF adoption, synthesizing recent evidence on resource consumption and emerging sustainability solutions in the context of the climate crisis facing nephrology. RECENT FINDINGS/RESULTS:Life cycle assessments indicate HDF has a carbon footprint 30-40% higher than conventional hemodialysis, consuming an additional 10 300 L of water per patient annually. However, recent technological innovations show promise: expanded hemodialysis (HDx) using medium cut-off membranes reduces water usage by >20% and energy consumption by >30% compared to HDF while potentially achieving similar clinical outcomes. Water conservation technologies, including reverse osmosis, reject water reuse and reduced dialysate flow protocols, can decrease environmental impact by 30-50% without any difference in patient outcomes. SUMMARY/CONCLUSIONS:The adoption of HDF represents a critical test case for sustainable healthcare innovation. While the potential benefits should not be ignored, technology is not static and, if confirmed, additional sustainability work and comprehensive policy frameworks integrating environmental impact assessments into technology evaluation are urgently needed. The nephrology community must balance clinical excellence with planetary stewardship through technological innovation, resource optimization, and evidence-based environmental guidelines that benefit, not compromise, patient care.