Does a multimethod approach improve identification of medication nonadherence in adolescents with chronic kidney disease?

BACKGROUND: Medical provider assessment of nonadherence is known to be inaccurate. Researchers have suggested using a multimethod assessment approach; however, no study has demonstrated how to integrate different measures to improve accuracy. This study aimed to determine if using additional measures improves the accurate identification of nonadherence beyond provider assessment alone. METHODS: Eighty-seven adolescents and young adults (AYAs), age 11-19 years, with chronic kidney disease (CKD) [stage 1-5/end-stage renal disease (ESRD)] and prescribed antihypertensive medication, their caregivers, and 17 medical providers participated in the multisite study. Five adherence measures were obtained: provider report, AYA report, caregiver report, electronic medication monitoring (MEMS), and pharmacy refill data [medication possession ratio (MPR)]. Concordance was calculated using kappa statistic. Sensitivity, specificity, positive predictive power, and negative predictive power were calculated using MEMS as the criterion for measuring adherence. RESULTS: There was poor to fair concordance (kappas = 0.12-0.54), with 35-61% of AYAs classified as nonadherent depending on the measure. While both providers and MEMS classified 35% of the AYAs as nonadherent, sensitivity (0.57) and specificity (0.77) demonstrated poor agreement between the two measures on identifying which AYAs were nonadherent. Combining provider report of nonadherence and MPR < 75% resulted in the highest sensitivity for identifying nonadherence (0.90) and negative predictive power (0.88). CONCLUSIONS: Nonadherence is prevalent in AYAs with CKD. Providers inaccurately identify nonadherence, leading to missed opportunities to intervene. Our study demonstrates the benefit to utilizing a multimethod approach to identify nonadherence in patients with chronic disease, an essential first step to reduce nonadherence.

Patient Health Beliefs and Characteristics Predict Longitudinal Antihypertensive Medication Adherence in Adolescents With CKD.

Objective: To investigate longitudinal associations of health beliefs, which included self-efficacy, outcome expectancies, and perceived barriers, and demographic risk factors (i.e., age, gender, race, and family income) with antihypertensive medication adherence in adolescents with chronic kidney disease (CKD) over 24 months. Method: The sample included 114 adolescents (M age = 15.03 years, SD = 2.44) diagnosed with CKD. Adolescents reported their self-efficacy for taking medications, medication outcome expectancies, and barriers to adherence at baseline and 12 and 24 months after baseline. Antihypertensive medication adherence was assessed via electronic monitoring for 2 weeks at baseline and 6, 12, 18, and 24 months after baseline. Results: Adherence increased and then decreased over the 2-year study period (inverted U-shape). Self-efficacy, outcome expectancies, and barriers did not change over time. Older adolescent age, female gender, African American race, <$50,000 annual family income, and public health insurance were associated with lower adherence. However, family income was the primary demographic risk factor that predicted adherence over time (≥$50,000 annual family income was longitudinally associated with higher adherence). Higher self-efficacy and more positive and less negative outcome expectancies across time were also associated with higher antihypertensive medication adherence across time. Conclusions: Clinical interventions should be developed to target medication self-efficacy and outcome expectancies to improve long-term antihypertensive medication adherence in adolescents with CKD. Family income may be considered when conceptualizing contextual factors that likely contribute to adolescents' consistent challenges with medication adherence over time.

Results of early treatment for de novo donor-specific antibodies in pediatric kidney transplant recipients in a cross-sectional and longitudinal cohort.

The development of dnDSA anti-HLA antibodies has been shown to be a significant risk factor for graft failure. In 2008, we instituted a routine protocol of standardized monitoring and treatment of dnDSA in pediatric kidney transplant recipients. Of 67 first-time pediatric kidney transplant recipients, 26 (38%) developed dnDSA after 1.36 (IQ 1-2.14) years. Coefficient of variance of tacrolimus, a surrogate marker of non-adherence, was found to be the single most important risk factor for dnDSA development. Overall, there was a significant reduction in dnDSA with treatment in 19 (76%) children. No difference in graft survival and estimated glomerular filtration rate was noted between dnDSA negative and those treated for dnDSA. There was an increased risk of hospitalization in those treated for dnDSA. This study suggests that early detection and treatment of dnDSA can help to prevent graft failure and preserve graft function in the short term. Future studies and longer follow-up are needed to fully elucidate the effect of early detection and treatment of dnDSA in pediatric kidney transplant recipients.

Dialysis in Children and Adolescents: The Pediatric Nephrology Perspective.

The care of children with end-stage renal disease (ESRD) is highly specialized and often poorly understood by nonpediatric providers and facility/institution administrators. As such, this position paper has been created to offer provider, facility, and institutional guidance regarding the components of care necessary for children receiving dialysis. Key differences between adult and pediatric dialysis units are highlighted. Responsibilities and expectations of the members of the interdisciplinary dialysis team are outlined as they pertain specifically to the care of pediatric dialysis patients. Physical and staffing requirements of the dialysis facility are reviewed, again focusing on unique needs and challenges faced by the pediatric dialysis care team. Among these, vascular access options and proper planning of ESRD care are underscored. Pediatric quality-of-life metrics differ significantly from adult quality variables, and proper tools for assessment must be used. Endorsed by the Council of the American Society of Pediatric Nephrology (ASPN), this position paper serves as a reference tool for the provision of care to pediatric patients with ESRD.

Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis.

Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na(+))-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH)2 vitamin D levels, hypercalciuria, and rickets/osteomalacia. Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable from those changes encountered in idiopathic hypercalciuria (IH). Here, we report a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified. Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46% compared with 6% observed in healthy family members carrying only the wild-type SLC34A3 allele (P=0.005) or 5.64% in the general population (P<0.001). Renal calcifications were also more frequent in het carriers (16%; P=0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (odds ratio [OR], 0.75, 95% confidence interval [95% CI], 0.59 to 0.96; P=0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95% CI, 0.23 to 0.72; P=0.002), and increased serum 1,25(OH)2 vitamin D (OR, 1.22; 95% CI, 1.05 to 1.41; P=0.008). Additional studies are needed to determine whether these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, CKD.

Late acute rejection: incidence, risk factors, and effect on graft survival and function.

Long-term graft survival and function has not kept pace with short-term success in kidney transplant (Tx) recipients. LAR ≥6 months post-Tx may contribute to lack of improvement; risk factors for LAR are not well known. Of 64 Tx recipients followed over six yr, 23 (35.9%) had LAR (LAR group) and 41 had no LAR (no LAR group). Of all variables, significant risk factors for LAR included DGF, (43.4% LAR vs. 14.6% in no LAR group, p = 0.0096); de novo DSA (65.2% vs. 26.8%, p = 0.003); mean COV% of TAC (41.8% vs. 34.6%, p = 0.03); and non-adherence (34.8% vs. 7.3%, p = 0.0043). DGF and DSA remained statistically significant (p = 0.002 and 0.003, respectively); COV% TAC had borderline significance (p = 0.057), and non-adherence was not significant on multivariate regression analysis. Patients with LAR had inferior graft survival and function, whereas graft function was stable in the no LAR group over a mean follow-up of 31.2 months. Patients with de novo DSA and DGF should be considered at risk of LAR; an early diagnosis and treatment of LAR may improve graft survival and function.

Development of an animal model of nephrocalcinosis via selective dietary sodium and chloride depletion.

BACKGROUND: Nephrocalcinosis (NC) is an important clinical problem seen in critically ill preterm neonates treated with loop diuretics. No reliable animal models are available to study the pathogenesis of NC in preterm infants. The purpose of this study was to develop a reproducible and clinically relevant animal model of NC for these patients and to explore the impact of extracellular fluid (ECF) volume contraction induced by sodium and chloride depletion in this process. METHODS: Three-week-old weanling Sprague-Dawley rats were fed diets deficient in either chloride or sodium or both. A subgroup of rats from each dietary group was injected daily with furosemide (40 mg/kg i.p.). RESULTS: Rats fed a control diet, with or without furosemide, or a chloride-depleted diet alone, did not develop NC. By contrast, 50% of the rats injected with furosemide and fed the chloride-depleted diet developed NC. Moreover, 94% of the rats fed the combined sodium- and chloride-depleted diet developed NC, independently of furosemide use. NC was associated with the development of severe ECF volume contraction; hypochloremic, hypokalemic, metabolic alkalosis; increased phosphaturia; and growth retardation. CONCLUSION: Severe ECF volume contraction induced by chronic sodium and chloride depletion appears to play an important role in the pathogenesis of NC.

Overcoming Barriers to Drug Development in Children with CKD.

Like all sick children, children with CKD need access to safe and effective medicines that have been formulated and examined specifically for them. Despite legislation in the United States and the European Union that either mandates or incentivizes programs for children, conducting trials to advance the treatment of children continues to prove to be a challenge for drug developers. This is also the case for drug development in children with CKD, where trials face challenges in recruitment and completion and where there remains a substantial time lag between initial approval of a medicinal product for use in adults and completion of studies that result in the addition of pediatric-specific labeling for the same indication. The Kidney Health Initiative commissioned a workgroup of diverse stakeholders ( https://khi.asn-online.org/projects/project.aspx?ID=61 ), including participants from the Food and Drug Administration and the European Medicines Agency, to think carefully through the challenges in drug development for children with CKD and how to overcome them. This article provides an overview of the regulatory frameworks in the United States and the European Union that govern pediatric drug development, the current landscape of drug development and approval for children with CKD, the challenges in conduct and execution of these drug trials, and the progress that has been made to facilitate drug development for children with CKD.

Severe hypercalcemia without hypercalciuria in a previously healthy infant.

Williams-Beuren syndrome (WBS) is a multisystem disorder that has a broad range of clinical findings including characteristic facial appearance, supravalvular aortic stenosis, dental and developmental abnormalities, and endocrinologic disorders including but not limited to the development of hypercalcemia. We present the case of a 10-month-old girl, with a history of intrauterine growth restriction, who presented with symptoms of weight loss and poor feeding. She was found to have severe elevation of her serum calcium to 20 mg/dL. She was subsequently diagnosed with WBS by fluorescent in situ hybridization analysis. The exact etiology of hypercalcemia in patients with WBS is unknown, but there are several hypotheses. Treatment of hypercalcemia in WBS is achieved with intravenous (IV) fluids, loop diuretics, and a low calcium diet; bisphosphonate therapy is required if adequate decreases in the serum calcium level are not achieved with traditional therapy.

Low bone mineral density and nutritional vitamin D deficiency in pediatric renal transplant recipients: Assessment of risk factors and response to oral vitamin D therapy.

VitD deficiency and bone disease are common after Tx. Prevalence and risk factors for low VitD and BMD and response to VitD therapy were investigated in pediatric renal Tx recipients. 25-hydroxy VitD levels of 71 Tx were compared to 54 healthy AA children. DXA of 44 Tx were compared to 47 AA controls. Of Tx, 59% were AA. Majority (59.1%) of Tx were VitD deficient (23.9%) or insufficient (35.2%). Prevalence of low VitD levels was double in AA (73.9%) vs. non-AA Tx (37.7%), (p = 0.003). Low VitD among Tx was associated with AA ethnicity (p < 0.01), winter (p < 0.05), older age (p < 0.05), males (p < 0.05) and time <6 months post Tx (p < 0.05). Tx with low VitD were treated with oral ergocalciferol or cholecalciferol (23 each); 13% treated with ergocalciferol vs. 82.6% treated with cholecalciferol achieved repletion (p < 0.0001). Of 36 Tx with whole body DXA, 19.5% had BMD (z < -1) after height adjustment. AA Tx had 3.4-fold higher risk of low BMD vs. controls (p < 0.05). Low VitD and BMD are prevalent in children after renal Tx. Better repletion of VitD is achieved with cholecalciferol.

Engagement and Affective Communication During Pediatric Nephrology Clinic Visits: Associations with Medication Adherence.

OBJECTIVE: To evaluate whether engagement and affective communication among adolescents and young adults (AYAs) with chronic kidney disease (CKD), caregivers, and pediatric nephrology providers during outpatient clinic visits predicts antihypertensive medication adherence. METHODS: AYAs (n = 60, M age = 15.4 years, SD = 2.7, 40% female, 43% African American/Black) and caregivers (n = 60, 73% female) attended audio-recorded clinic visits with pediatric nephrologists (n = 12, 75% female). Recordings were analyzed using global affect ratings of the Roter Interactional Analysis System. Antihypertensive medication adherence was monitored electronically before and after clinic visits. A linear regression model evaluated associations between affect ratings and post-visit adherence. RESULTS: AYAs took 84% of doses (SD = 20%) pre-visit and 82% of doses (SD = 24%) post-visit. Higher AYA engagement (ß = 0.03, p = .01) and the absence of provider negative affect (ß=-0.15, p = .04) were associated with higher post-visit adherence, controlling for pre-visit adherence, AYA sex, age, and race, and clustered by provider. CONCLUSIONS: Post-visit adherence was higher when AYAs were rated as more engaged and providers as less negative. PRACTICE IMPLICATIONS: AYAs with lower engagement may benefit from further adherence assessment. Communication strategies designed to more actively engage AYAs in their care and diminish provider conveyance of negative affect during clinic visits may positively influence adherence among AYAs with CKD.

Vitamin D deficiency and parathyroid hormone levels following renal transplantation in children.

The objectives were to determine the prevalence of vitamin D deficiency [25(OH)D < 10 ng/ml] in pediatric renal transplant (RTx) recipients, compared with controls and identify correlates of changes in 25(OH)D and intact parathyroid hormone (iPTH) levels following transplantation. Serum 25(OH)D, 1,25(OH)(2)D, and iPTH were measured once in 275 healthy controls and at transplantation, and 3 and 12 months posttransplantation in 58 RTx recipients. Multivariate logistic regression models determined the odds ratio (OR) of vitamin D deficiency in RTx recipients vs. controls adjusted for age, sex, race, and season. Generalized estimating equations were used to assess changes following transplantation. At transplantation, 22% of nonblack and 27% of black RTx recipients were vitamin D deficient. The adjusted OR of vitamin D deficiency was greater in RTx recipients (p < 0.001) compared with controls; however, the transplant association was greater in nonblack vs. black individuals (interaction p = 0.02). Overall, 25(OH)D levels did not change significantly following transplantation. Younger age (p < 0.01), nonblack race (p < 0.001), visits in nonwinter months (p < 0.001), and supplementation with ≥400 IU/day ergo/cholecalciferol (p < 0.001) were associated with increases (or lesser declines) in 25(OH)D following transplantation. Increases in 25(OH)D levels (p < 0.001) and vitamin D supplementation (p < 0.01) were associated with greater reductions in iPTH levels following transplantation, independent of 1,25(OH)(2)D levels.

Rituximab in refractory nephrotic syndrome.

The aim of this study was to establish the efficacy and safety of rituximab in refractory nephrotic syndrome (NS). Members of the International Paediatric Nephrology Association were asked to retrospectively fill in a questionnaire with details on the use of rituximab in their centres. We divided the data into three groups: group 1, patients with steroid-dependent and frequently relapsing NS; group 2, with steroid-resistant NS; group 3, with post-transplant recurrence of NS. Seventy questionnaires from 25 centres described the outcome of 28, 27 and 15 patients in groups 1, 2 and 3, respectively. Of these, 82% of patients in group 1, 44% of patients in group 2 and 60% of patients in group 3 had a good initial response. Side effects were observed in 27% of the patients, and these were mostly acute reactions. We present a large multicentre series of children with refractory NS. Children in group 1 showed the best response. The good initial response in group 3 can be biased by the accompanying treatments that were administered at the same time as rituximab. Controlled prospective trials are required to establish the value of rituximab in idiopathic NS.

HIV-Associated CKDs in Children and Adolescents.

INTRODUCTION: Limited information is available describing the current prevalence of proteinuria and HIV-associated CKDs (HIV-CKDs) in children and adolescents living with HIV and receiving antiretroviral therapy in the United States. METHODS: To address this issue, we performed a retrospective study of children and adolescents living with HIV who received medical care at Children's National Hospital in Washington, DC, between January 2012 and July 2019. Demographic data, clinical parameters (mode of HIV transmission, viral loads, CD4 cell counts, serum creatinine, glomerular filtration rate [GFR], plasma lipid levels, proteinuria, blood pressure, renal biopsies), and medical treatments, all done as a standard of clinical care, were collected and analyzed. RESULTS: The majority of the 192 patients enrolled were of African descent (88%) and acquired HIV through vertical transmission (97%). The prevalence of all HIV-CKDs was 6%. Of these patients, 39% had intermittent or persistent proteinuria, and 7% percent had proteinuria with a mild decline in GFR (60-80 ml/min per 1.73 m2), and 6% had a mild decline in GFR without proteinuria. Documented hypertension was present in 6% of the patients, mainly in association with HIV-CKD. Patients with persistent proteinuria (3%) and biopsy-proven HIV-CKD had a slow but constant progression of their renal diseases. CONCLUSIONS: The prevalence of persistent proteinuria and HIV-CKD was lower than that reported in previous studies conducted in the United States. However, intermittent proteinuria, mild reductions in GFR, and progression of established HIV-CKD were common findings in this group of patients with predominantly vertically acquired HIV who were receiving antiretroviral therapy.

Executive functioning, caregiver monitoring, and medication adherence over time in adolescents with chronic kidney disease.

OBJECTIVE: The purpose of this study was to evaluate associations between executive functioning and caregiver adherence monitoring with objective antihypertensive medication adherence over 24 months in adolescents with chronic kidney disease (CKD). METHODS: Adolescents (N = 97, 11-20 years old) with CKD taking antihypertensive medication and their caregivers were recruited from three pediatric nephrology clinics. At baseline, adolescents and caregivers reported on adolescents' executive functioning and caregivers reported on their adherence monitoring. Antihypertensive medication adherence was objectively assessed via electronic monitoring at baseline and every 6 months after for 24 months. Associations between executive functioning, caregiver monitoring, and longitudinal adherence were evaluated with linear mixed models. RESULTS: Up to 38% of adolescents had elevated executive functioning scores indicating more severe impairments, with rates varying by scale and reporter (adolescent vs. caregiver). Caregiver monitoring showed a significant, negative association with adherence, but adolescents' executive functioning was not significantly associated with adherence. Neither variable was associated with the rate of change in adherence over time. CONCLUSIONS: Given that adolescents' executive functioning was not associated with antihypertensive medication adherence or changes in adherence over time, adherence to daily pill-form medications may involve less cognitive effort than more complex medical regimens. Higher levels of caregiver monitoring were unexpectedly associated with lower adherence levels. This unanticipated finding may reflect increased caregiver monitoring efforts when faced with adolescents' medication nonadherence, but this finding warrants further investigation. Adolescents with CKD who are nonadherent may benefit from medication adherence-promoting strategies beyond increasing caregiver monitoring. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Evaluating provider communication in pediatric chronic kidney disease care using a global coding system.

OBJECTIVE: Among adolescents and young adults (AYAs) with chronic illness, effective provider communication is essential for patient-centered care during a sensitive developmental period. However, communication in chronic illness care for AYAs is not well studied. Our objectives were to describe the provider communication skills in pediatric chronic kidney disease (CKD) care visits; and determine if communication skills differ by AYA characteristics. METHODS: We adapted a global consultation rating system for pediatric subspecialty care using audiotaped clinic encounters of 18 pediatric nephrologists with 99 AYAs (age M(SD) = 14.9(2.6)) with CKD stages 1-5 and 96 caregivers. We hypothesized that provider communication skills would differ by AYA characteristics (age, gender, and race). RESULTS: The strongest provider skills included initiating the session and developing rapport; lowest rated skills were asking patient's perspective and checking understanding. Communication scores did not consistently differ by AYA age or race, but were rated higher with female AYAs in several domains (ps<0.05). CONCLUSIONS: Pediatric providers generally had adequate or good communication scores with AYAs, but improvement in certain skills, particularly with male AYAs, may further support patient-centered care. PRACTICE IMPLICATIONS: To achieve consistent, patient-centered communication with AYAs, an observation-based global assessment may identify areas for provider improvement.

Elevated urine oxalate and renal calculi in a classic galactosemia patient on soy-based formula.

Classic galactosemia results from a deficiency in the galactose-1-phosphate uridylyltransferase (GALT) enzyme, which is essential for galactose metabolism. Treatment focuses on lactose restriction and is achieved with a soy-based diet. Previously, renal calculi have not been documented in galactosemia patients. We present a patient with galactosemia nutritionally dependent on soy-based formula via G-tube, who developed renal calculi. Analysis of urinary stone risk factors revealed elevated urine oxalate levels and stone analysis confirmed calcium oxalate composition. Initiation of lactose- and soy-free elemental formula returned urine oxalate level to normal. Given the presence of a metabolic pathway for the conversion of galactose to oxalate, and the high content of oxalate in soy-based formula, there is the potential for elevated urine oxalate and a resulting risk of urinary calculi formation in patients with classic galactosemia. This potential can be effectively managed with a lactose and soy-free elemental diet. This report describes the clinical course and novel findings of calcium oxalate urinary calculi in a classic galactosemia patient dependent upon soy-based formula, with a discussion regarding the multiple factors leading to increased stone formation in this patient.

Interpretation of biomarkers of bone metabolism in children: impact of growth velocity and body size in healthy children and chronic disease.

OBJECTIVES: To determine the effects of growth, maturation, and whole body bone mineral content (WB-BMC) accrual on biomarkers of bone formation (bone-specific alkaline phosphatase [BSAP]) and resorption (urine deoxypyridinoline/creatinine [DPD]) in healthy children and children with Crohn's disease. STUDY DESIGN: BSAP and DPD were measured at baseline, with growth and dual energy x-ray absorptiometry (DXA) WB-BMC measured at baseline and 6 months in 202 control subjects and 110 subjects with Crohn's disease, ages 5 to 21 years. Multivariable linear regression identified determinants of biomarkers in control subjects and subjects with Crohn's disease. RESULTS: In control subjects, BSAP and DPD were significantly and independently associated with sex, Tanner stage, WB-BMC, height velocity, and WB-BMC accrual rates; these covariates explained 77% to 80% of the variability in the bone biomarkers, respectively. Subjects with Crohn's disease had lower height-for-age (P < .001) and WB-BMC-for-height (P <.05) than control subjects. Crohn's disease was associated with lower BSAP (P < .001) and greater DPD (P < .001), independent of growth, maturation, baseline WB-BMC, and WB-BMC accrual, compared with control subjects. CONCLUSIONS: These data illustrate the potential confounding effects of growth and WB-BMC on bone metabolism biomarkers in children. After adjustment for these effects, Crohn's disease was associated with lower biomarkers of bone formation and greater bone resorption.

Treatment challenges in an atypical presentation of tubulointerstitial nephritis and uveitis (TINU).

PURPOSE: To describe an atypical presentation of Tubulointerstitial Nephritis and Uveitis (TINU), with challenges in treatment course. OBSERVATIONS: A 12-year-old Hispanic female presented to the National Eye Institute's Uveitis clinic with bilateral blurred vision, red eyes and photophobia, not responsive to topical steroids. On exam, she had bilateral severe panuveitis with areas of subretinal fluid. During her evaluation, she was noted to have elevated serum creatinine. A kidney biopsy confirmed the presence of severe tubulointerstitial nephritis and interstitial fibrosis. She was treated with oral steroids with excellent resolution of symptoms and subretinal fluid. She continued to have anterior segment flares with attempts to taper oral prednisone which lead to treatment with multiple immunomodulatory agents. Associated hypertension and kidney damage complicated the choice of a secondary immunosuppressive agent. CONCLUSIONS AND IMPORTANCE: Although rare, TINU can present as panuveitis with choroidal involvement which may or may not be preceded by tubulointerstitial nephritis. A renal biopsy is required for definitive diagnosis, but abnormal urinalysis or renal function should raise suspicion for TINU.