Medical management for the prevention of kidney stones.

The alarming fact is that approximately one out of every 10 of us will have a kidney stone during our lifetime. The increasing prevalence and associated costs of kidney stones have resulted in it being one of the most commonly encountered and impactful medical conditions. Contributing factors include, but are not limited to, diet, climate, genetics, medications, activity and underlying medical conditions. Symptoms generally parallel stone size. Treatment varies from supportive to procedural (invasive and non-invasive). Prevention remains the best way to avoid this condition especially given the high recurrence rate. First time stone formers require counselling regarding dietary adjustments. Certain risk factors ultimately require a more in-depth metabolic investigation, especially if stones are recurrent. Ultimately, management is defined by stone composition. Where appropriate, we review both pharmacologic and non-pharmacologic options. Pivotal to successful prevention is patient education and the encouragement of compliance with the appropriate regimen.

Hypoxia-inducible factor stabilizers: 27 228 patients studied, yet a role still undefined.

With the emergence of hypoxia inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) came the hope that using these oral drugs could improve the treatment of the anemia of kidney disease. In this editorial we discuss the accumulated knowledge on these agents and the clinical context for use.

Complement Inhibitors in the Management of Complement-Mediated Hemolytic Uremic Syndrome and Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: Complement-mediated HUS (CM-HUS) and paroxysmal nocturnal hemoglobinuria (PNH) are rare hematologic disorders that cause dysregulation and hyperactivation of the complement system. Historically, treatment of CM-HUS involved plasma exchange (PLEX), often with limited benefit and variable tolerance. Conversely, PNH was treated with supportive care or hemopoietic stem cell transplant. Within the last decade, monoclonal antibody therapies that block terminal complement pathway activation, have emerged as less invasive and more efficacious options for management of both disorders. This manuscript seeks to discuss a relevant clinical case of CM-HUS and the evolving landscape of complement inhibitor therapies for CM-HUS and PNH. AREAS OF UNCERTAINTY: Eculizumab, the first humanized anti-C5 monoclonal antibody, has been the standard of care in treating CM-HUS and PNH for over a decade. Although eculizumab has remained an effective agent, the variability in ease and frequency of administration has remained an obstacle for patients. The development of novel complement inhibitor therapies with longer half-lives, has allowed for changes in frequency and route of administration, thus improving patient QOL. However, there are limited prospective clinical trial data given disease rarity, and limited information on variable infusion frequency and length of treatment. THERAPEUTIC ADVANCES: Recently, there has been a push to formulate complement inhibitors that improve QOL while maintaining efficacy. Ravulizumab, a derivative of eculizumab, was developed to allow for less frequent administration, while remaining efficacious. In addition, the novel oral and subcutaneous therapies, danicopan and crovalimab, respectively, along with pegcetacoplan are currently undergoing active clinical trials, and poised to further reduce treatment burden. CONCLUSION: Complement inhibitor therapies have changed the treatment landscape for CM-HUS and PNH. With a significant emphasis on patient QOL, novel therapies continue to emerge and require an in-depth review of their appropriate use and efficacy in these rare disorders. CLINICAL CASE: A 47-year-old woman with hypertension and hyperlipidemia presented with shortness of breath and was found to have hypertensive emergency in the setting of acute renal failure. Her serum creatinine was 13.9 mg/dL; elevated from 1.43 mg/dL 2 years before. The differential diagnosis for her acute kidney injury (AKI) included infectious, autoimmune, and hematologic processes. Infectious work-up was negative. ADAMTS13 activity level was not low at 72.9%, ruling out thrombotic thrombocytopenic purpura (TTP). Patient underwent a renal biopsy, which revealed acute on chronic thrombotic microangiopathy (TMA). A trial of eculizumab was initiated with concurrent hemodialysis. The diagnosis of CM-HUS was later confirmed by a heterozygous mutation in complement factor I (CFI), resulting in increased membrane attack complex (MAC) cascade activation. The patient was maintained on biweekly eculizumab and was eventually transitioned to ravulizumab infusions as an outpatient. Her renal failure did not recover, and the patient remains on hemodialysis while awaiting kidney transplantation.

Breaking the Cycle of Recurrent Calcium Stone Disease.

Calcium stones are common and recurrent in nature, yet few therapeutic tools are available for secondary prevention. Personalized approaches for stone prevention have been informed by 24-hour urine testing to guide dietary and medical interventions. However, current evidence is conflicting about whether an approach guided by 24-hour urine testing is more effective than a generic one. The available medications for stone prevention, namely thiazide diuretics, alkali, and allopurinol, are not always prescribed consistently, dosed correctly, or tolerated well by patients. New treatments on the horizon hold the promise of preventing calcium oxalate stones by degrading oxalate in the gut, reprogramming the gut microbiome to reduce oxalate absorption, or knocking down expression of enzymes involved in hepatic oxalate production. New treatments are also needed to target Randall's plaque, the root cause of calcium stone formation.

Recovery of Severe Acute Kidney Injury in a Patient with COVID-19: Role of Lung Ultrasonography.

Acute kidney injury (AKI) is recognized as a complication of COVID-19 among hospitalized patients. Lung ultrasonography (LUS) can be a useful tool in the management of COVID-19 pneumonia when interpreted correctly. However, the role of LUS in management of severe AKI in the setting of COVID-19 remains to be defined. We report a 61-year-old male who was hospitalized with acute respiratory failure from COVID-19 pneumonia. In addition to requiring invasive mechanical ventilation, our patient developed AKI and severe hyperkalemia requiring urgent dialytic therapy during his hospital stay. Our patient remained dialysis dependent despite subsequent recovery of lung function. Three days following discontinuation of mechanical ventilation, our patient developed a hypotensive episode during his maintenance hemodialysis treatment. A point of care LUS performed soon after the intradialytic hypotensive episode found no extravascular lung water. Hemodialysis was discontinued and the patient was initiated on intravenous fluids for one week. AKI subsequently resolved. We consider LUS an important tool in identifying COVID-19 patients that would benefit from intravenous fluids following recovery of lung function.

Medical management for the prevention of kidney stones.

The alarming fact is that approximately one out of every 10 of us will have a kidney stone during our lifetime. The increasing prevalence and associated costs of kidney stones have resulted in it being one of the most commonly encountered and impactful medical conditions. Contributing factors include, but are not limited to, diet, climate, genetics, medications, activity and underlying medical conditions. Symptoms generally parallel stone size. Treatment varies from supportive to procedural (invasive and non-invasive). Prevention remains the best way to avoid this condition especially given the high recurrence rate. First time stone formers require counselling regarding dietary adjustments. Certain risk factors ultimately require a more in-depth metabolic investigation, especially if stones are recurrent. Ultimately, management is defined by stone composition. Where appropriate, we review both pharmacologic and non-pharmacologic options. Pivotal to successful prevention is patient education and the encouragement of compliance with the appropriate regimen.

Outcomes Among Patients Hospitalized With COVID-19 and Acute Kidney Injury.

RATIONALE & OBJECTIVE: Outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) are not well understood. The goal of this study was to investigate the survival and kidney outcomes of these patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients (aged≥18 years) hospitalized with COVID-19 at 13 hospitals in metropolitan New York between March 1, 2020, and April 27, 2020, followed up until hospital discharge. EXPOSURE: AKI. OUTCOMES: Primary outcome: in-hospital death. SECONDARY OUTCOMES: requiring dialysis at discharge, recovery of kidney function. ANALYTICAL APPROACH: Univariable and multivariable time-to-event analysis and logistic regression. RESULTS: Among 9,657 patients admitted with COVID-19, the AKI incidence rate was 38.4/1,000 patient-days. Incidence rates of in-hospital death among patients without AKI, with AKI not requiring dialysis (AKI stages 1-3), and with AKI receiving dialysis (AKI 3D) were 10.8, 31.1, and 37.5/1,000 patient-days, respectively. Taking those without AKI as the reference group, we observed greater risks for in-hospital death for patients with AKI 1-3 and AKI 3D (HRs of 5.6 [95% CI, 5.0-6.3] and 11.3 [95% CI, 9.6-13.1], respectively). After adjusting for demographics, comorbid conditions, and illness severity, the risk for death remained higher among those with AKI 1-3 (adjusted HR, 3.4 [95% CI, 3.0-3.9]) and AKI 3D (adjusted HR, 6.4 [95% CI, 5.5-7.6]) compared with those without AKI. Among patients with AKI 1-3 who survived, 74.1% achieved kidney recovery by the time of discharge. Among those with AKI 3D who survived, 30.6% remained on dialysis at discharge, and prehospitalization chronic kidney disease was the only independent risk factor associated with needing dialysis at discharge (adjusted OR, 9.3 [95% CI, 2.3-37.8]). LIMITATIONS: Observational retrospective study, limited to the NY metropolitan area during the peak of the COVID-19 pandemic. CONCLUSIONS: AKI in hospitalized patients with COVID-19 was associated with significant risk for death.

Opportunities for Subspecialization in Nephrology.

The interface between nephrology and other fields of medicine continues to expand. With the advent of novel therapies in cancer, diagnostics and therapeutics in lithology, novel devices in cardiology, advances in women's health issues, novel diagnostics and therapies in glomerular diseases, and the national priority in home-based dialysis, several subspecialties in nephrology have emerged. This article will discuss the subspecialties of onconephrology, cardionephrology, obstetric nephrology, uronephrology, glomerular disease specialization, and home-based dialysis in nephrology. We discuss the current state of each subspecialty, recommended educational content, length of training, available training opportunities, and potential career pathways for each.

Kidney oxalate crystal deposition in adult patients: A relatively common finding
.

AIMS: We aim to describe the clinical and histological findings in patients with the finding of any tubular oxalate deposits in kidney biopsy specimens. BACKGROUND: The prevalence, manifestation, and outcome of secondary oxalate nephropathy have not been extensively studied. MATERIALS AND METHODS: In this retrospective cohort study, we analyzed the clinical and histological findings in all patients with the finding of any tubular oxalate deposits in kidney biopsy specimens between July 1, 2017, and December 31, 2018, at Northwell Health Pathology Department (Manhasset, NY, USA). RESULTS: The prevalence of oxalate deposition on a kidney biopsy was 4.07% (25/615), and in 88% of cases was a major finding. Prior to biopsy, oxalate was anticipated in only 1 case. The etiology of oxalosis was clarified retrospectively in 14 cases, most commonly due to GI surgery (n = 10) and increased oxalate intake (n = 4). In 11 cases, etiology remained unknown, although at least 3 cases were exposed to antibiotics associated with secondary oxalosis. There was no significant clinical/pathological or survival difference between known vs. unknown cause groups. The overall 3-month renal survival rate was 76.0 ± 8.5%. Multivariate Cox regression showed that creatinine at the time of biopsy (HR: 1.79, 95% CI: 0.71 - 4.51), background histological chronicity change (HR: 1.82, 95% CI: 0.70 - 4.72) and oxalate density (HR: 2.27, 95% CI: 0.49 - 10.55) are associated with end-stage kidney disease. CONCLUSION: Oxalate deposition is common but rarely anticipated biopsy finding. Nephrologists need to consider surgical history and other secondary causes of oxalosis as causes of acute kidney injury and chronic kidney disease.

Occupational kidney stones.

PURPOSE OF REVIEW: Kidney stones are a common and preventable disorder. Certain occupations may increase risk for stone disease which will be discussed in this review. Few observational studies have examined this association. RECENT FINDINGS: Some occupations prevent individuals from drinking enough fluids to maintain a dilute urine or to void when they need to. People may have poor access to fluids or to bathroom facilities. These issues pose a risk for stone disease and are exacerbated by those who work in warmer climates. Individuals who do more activity while working, especially outdoors, perspire more, leading to more concentrated urine. In more sedentary jobs, individuals are at a higher risk of metabolic syndrome and therefore have a higher risk for stones. Astronauts, who work in environments without gravity, mobilize calcium from bone, leading to a higher risk of stone disease. SUMMARY: Proper fluid intake, more access to restrooms and increased use of potassium citrate may be the best options for those who encounter greater risk for stones because of their occupation.

Effect of increasing doses of cystine-binding thiol drugs on cystine capacity in patients with cystinuria.

Appropriate dosing of cystine-binding thiol drugs in the management of cystinuria has been based on clinical stone activity. When new stones form, the dose is increased. Currently, there is no method of measuring urinary drug levels to guide the titration of therapy. Increasing cystine capacity, a measure of cystine solubility, has been promoted as a method of judging the effects of therapy. In this study, we gave increasing doses of tiopronin or D-penicillamine, depending on the patients' own prescriptions, to ten patients with cystinuria and measured cystine excretion and cystine capacity. The doses were 0, 1, 2, 3 g per day, given in two divided doses, and administered in a random order. Going from 0 to 1 g/day led to an increase in cystine capacity from - 39.1 to 130.4 mg/L (P < 0.009) and decreased 24 h cystine excretion from 1003.9 to 834.8 mg/day (P = 0.039). Increasing the doses from 1 to 2 to 3 g/day had no consistent or significant effect to further increase cystine capacity or decrease cystine excretion. Whether doses higher than 1 g/day have additional clinical benefit is not clear from this study. Limiting doses might be associated with fewer adverse effects without sacrificing the benefit of higher doses if higher doses do not offer clinical importance. However, trials with stone activity as an outcome would be desirable.