Faculty Bibliography

Primary hyperoxaluria (PH) is a family of ultra-rare, autosomal recessive, metabolic disorders associated with frequent kidney stones, chronic kidney disease and kidney failure, and serious complications due to systemic oxalosis, resulting in significant morbidity. We investigated the burden of PH among affected patients and caregivers. This cross-sectional, web-based survey was used to quantify the burden of PH, in terms of healthcare resource utilization, health-related quality of life, and work productivity and activity impairment among adults (≥ 18 years) with PH and caregivers of children (≤ 17 years) with PH in the US. Among the 20 respondents, there were 7 adults with PH and 13 caregivers of children with PH. Adherence to hyperhydration was noted as the most, or one of the most, difficult aspects of PH by 56% of respondents. Most patients (95%) had experienced painful kidney stone events, one-third had visited the emergency room, and 29% were hospitalized for complications due to PH. Of the 24% of patients on dialysis, all found the procedure burdensome. Adult patients' quality of life was negatively affected across several domains. Most respondents (81%) reported that PH had a negative effect on their finances. Employed adult patients and caregivers, and children with PH, had moderate impairment in work productivity, school attendance, and activity. Anxiety about future PH-related sequelae was moderate to high. These findings highlight the need for improvements in PH medical management. A plain language summary is available in the supplementary information.

BACKGROUND: Primary hyperoxaluria (PH) is a family of rare genetic disorders affecting 1-3 per 1 million persons globally. PH causes hepatic oxalate overproduction leading to increased urinary oxalate excretion, that can result in frequent kidney stone events, progression to end-stage kidney disease (ESKD) and then other systemic morbidities.
OBJECTIVE(S): To assess the burden of PH among patients and caregivers with respect to healthcare resource utilization (HRU), quality of life (QoL) and work productivity.
METHOD(S): An IRB-approved web survey was conducted among adults (>= 18 years) with PH, and caregivers of children (< 17 years) with PH in the US. Participants were asked about their or their child's medical care, HRU and QoL. The Kidney Disease Quality of Life (KDQOL-36TM: range 0-100, higher score = better QOL) and Work Productivity and Activity Impairment (WPAI: range 0-100%, higher score = more impairment) questionnaires were administered. Descriptive statistics summarized the responses.
RESULT(S): Patient sample (n = 21) comprised 7 adults (median age 42 years) and 14 children (median age 8 years). Patients' HRU consisted of visits to nephrologists (81%), urologists (67%) and ophthalmologists (10%). 33% visited the emergency room and 29% were hospitalized. Patients on dialysis (n = 5) spent a median of 24 hours per week receiving dialysis. PH complications included kidney stone events (95%), pain (71%, nearly all moderate-severe) and nephrocalcinosis (48%). 48% of all patients experienced PH-related anxiety. Adult patients' mean KDQOL-36TM domain scores (burden, symptoms/problems and effects of kidney disease) were 38 (SD = 23), 77 (SD = 23) and 65 (SD = 26), respectively. Employed adult patients (n = 4) reported 25% presenteeism (reduced productivity at work) on average based on the WPAI. Children missed a median of 15 hours/month of school due to their PH. Caregivers (n = 13) experienced moderate-severe anxiety about the possibility of future PH-related outcomes (i.e., kidney stones [54%], kidney disease progression [62%] and ESKD [62%]) for their child. Employed caregivers (n = 9) reported 28% presenteeism on average based on the WPAI.
CONCLUSION(S): This research quantifies the burden of PH in terms of HRU, QoL and productivity for patients and caregivers. Patients experienced considerable clinical sequalae associated with PH, such as kidney stones and pain, which appear to negatively affect these outcomes. Numerous clinician visits indicated an intensive level of care. Further, PH burden goes beyond the patient, as evidenced by caregiver burden, including anxiety and impact on work productivity

Background: Potassium citrate is a mainstay of treatment to prevent recurrent calcium-containing kidney stones. However, it can increase urine pH and calcium phosphate (CaP) supersaturation (SS). HCA, extracted from Garcinia cambogia, is a potent inhibitor of calcium oxalate crystal growth in vitro and should not provide "potential base", as citrate does. Urine excretion of HCA has not been well-studied.
Method(s): We enrolled 2 groups: calcium stone formers (SF; n = 9) and non-stone forming (NSF, n = 9) controls (after excluding 2 SF and 2 NSF whose urine creatinine excretion on the 2 collections differed by more than 20%). Mean age 49.3 years. Thiazides and citrate were held for 2 weeks prior to study. Participants recorded a self-selected diet for 2 days and performed 24-hour urine collection on day 2. HCA was purchased online from Amazon.com (Super CitriMax Garcinia Cambogia); 2 caps = 900 mg of HCA. Participants took 900 mg 3 times daily orally for 7 days. Diet from days 1 and 2 was replicated on day 6 and 7 of the HCA arm of the study. 24-hour urine was collected on day 7. Urine was sent to Litholink, Inc. (Chicago, IL) for analysis. Urinary excretion of hydroxycitrate and citrate were measured using LC/MS.
Result(s): According to label, 6 pills would provide 2700 mg (13.2 mmol) of HCA per day; we measured content as 3198 mg (15.6 mmol). Citrate content is supposed to be 0, but we found 126 mg (0.66 mmol) per day. Both NSF and SF had appearance of HCA in the urine: 1.86 +/- 0.80 and 2.07 +/- 0.67 mmol/day (p = 0.56). Urine chemistry seen in Table 1. In NSF, pH and citrate did not change. In SF, pH increased, citrate did not. K went up in both groups.
Conclusion(s): Administration of HCA, a potential inhibitor of Ca stone formation, leads to significant urinary HCA excretion. Citrate excretion was not affected. Urine pH increased, suggesting some alkalinizing effect. The difference in NSF and SF may be due to the lower starting pH in SF. The effect of HCA on stone formation remains to be determined. (Figure Presented)

Cystinuria comprises less than 1% of kidney stones and is associated with impaired health-related quality of life (HRQOL). Limited evidence is available regarding HRQOL of patients with cystinuria treated with tiopronin (Thiola^®). The objective of this study was to assess the HRQOL of patients with or without tiopronin treatment. For this cross-sectional survey, patients on tiopronin treatment were recruited through the "Thiola^® Total Care Hub," a specialty pharmacy used to dispense tiopronin, and compared with patients not taking tiopronin (non-tiopronin group) who were identified from the Cystinuria Contact Registry at New York University School of Medicine. Consented patients responded to a survey that included questions about their experiences with kidney stones, the Wisconsin stone quality of life (WISQOL) (disease-specific) questionnaire, and the short form-36 version 2 (SF-36v2) (generic) HRQOL questionnaire. Statistical analyses included independent-sample t tests, one-way analysis of variance (ANOVA), and correlations. The survey was completed by 312 patients: 267 in the tiopronin group (144 male, 123 female; mean 49 years) and 45 in the non-tiopronin group (10 male, 35 female; mean 48 years). Both groups utilized pain medications similarly (24% overall). Patients on tiopronin had a significantly better HRQOL than patients not on tiopronin for all WISQOL domains (p < 0.001) and all but the physical functioning SF-36v2 domain (p < 0.001), where both groups approached the US normative mean, when controlling for the last stone event. Compared with patients in the non-tiopronin group, patients taking tiopronin reported better HRQOL on both the WISQOL and SF-36v2.

Background/UNASSIGNED:Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). Methods/UNASSIGNED:FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. Results/UNASSIGNED: 0.03). Conclusions/UNASSIGNED:PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.

BACKGROUND:A scarcity of organs has driven the transplant community to broaden selection criteria for both living and deceased donors. Living donor transplants offer better patient and allograft survival when compared with deceased donor transplants. Many transplant centers now allow complex living donors such as those with nephrolithiasis to undergo nephrectomy. METHODS:We conducted a survey of medical and surgical directors of kidney transplant programs in the United States to shed light on current practices pertaining to medical evaluation of living kidney donors with nephrolithiasis. 353 surveys were e-mailed to medical directors and surgical directors of transplant programs after contacts were obtained from UNOS. RESULTS:49 completed surveys were returned (13.9%). 77.7% (38/49) of survey participants said their centers will consider living kidney donor candidates with a history of symptomatic kidney stones, 69.4% (34/49) said their centers will consider candidates who are incidentally found to have kidney stones and 10.2% (5/49) said their centers decline all potential donors with nephrolithiasis. CONCLUSIONS:Several programs are still reluctant to allow potential donors with nephrolithiasis to donate. There is an unmet need to develop evidence-based guidelines to optimize outcomes in this population of kidney donors with nephrolithiasis and their recipients.