A Case Report of Mediastinal Teratoma in a Pediatric Patient With Nephrotic Syndrome: Paraneoplastic Syndrome or Incidental Finding?

A 12-year-old female presented with weight gain, edema, and shortness of breath. Laboratory and urine studies confirmed nephrotic syndrome and presence of a mediastinal mass, identified as a mature teratoma after resection. Nephrotic syndrome persisted despite resection and renal biopsy confirmed minimal change disease, which ultimately responded to steroid treatment. She had two relapses of nephrotic syndrome after vaccination administration, both of which occurred within eight months of tumor resection and were responsive to steroids. Autoimmune and infectious workup for other causes of nephrotic syndrome was negative. This is the first reported case of nephrotic syndrome associated with mediastinal teratoma.

Epidemiology and Risk Factors for Hemodialysis Access-Associated Infections in Children: A Prospective Cohort Study From the SCOPE Collaborative.

RATIONALE & OBJECTIVE: Infections cause significant morbidity and mortality for children receiving maintenance hemodialysis (HD). The Standardizing Care to Improve Outcomes in Pediatric End-Stage Kidney Disease (SCOPE) Collaborative is a quality-improvement initiative aimed at reducing dialysis-associated infections by implementing standardized care practices. This study describes patient-level risk factors for catheter-associated bloodstream infections (CA-BSIs) and examines the association between dialysis center-level compliance with standardized practices and risk of CA-BSI. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Children enrolled in SCOPE between June 2013 and July 2019. EXPOSURES: Data were collected on patient characteristics and center-level compliance with HD catheter care practices across the study period. Centers were categorized as consistent, dynamic (improved compliance over the study period), or inconsistent performers based on frequency of compliance audit submission and changes in compliance with HD care practices over time. OUTCOME: CA-BSIs. ANALYTICAL APPROACH: Generalized linear mixed models were used to evaluate (1) patient-level risk factors for CA-BSI and (2) associations between change in center-level compliance and CA-BSIs. RESULTS: The cohort included 1,277 children from 35 pediatric dialysis centers; 1,018 (79.7%) had a catheter and 259 (20.3%) had an arteriovenous fistula or graft. Among children with a catheter, mupirocin use at the catheter exit site was associated with an increased rate of CA-BSIs (rate ratio [RR], 4.45; P = 0.004); the use of no antibiotic agent at the catheter exit site was a risk factor of borderline statistical significance (RR, 1.79; P = 0.05). Overall median compliance with HD catheter care practices was 87.5% (IQR, 77.3%-94.0%). Dynamic performing centers showed a significant decrease in CA-BSI rates over time (from 2.71 to 0.71 per 100 patient-months; RR, 0.98; P < 0.001), whereas no significant change in CA-BSI rates was detected among consistent or inconsistent performers. LIMITATIONS: Lack of data on adherence to HD care practices on the individual patient level. CONCLUSIONS: Improvement in compliance with standardized HD care practices over time may lead to a reduction in dialysis-associated infections.

Identifying key predictors of mortality in young patients on chronic haemodialysis-a machine learning approach.

BACKGROUND: The mortality risk remains significant in paediatric and adult patients on chronic haemodialysis (HD) treatment. We aimed to identify factors associated with mortality in patients who started HD as children and continued HD as adults. METHODS: The data originated from a cohort of patients <30 years of age who started HD in childhood (≤19 years) on thrice-weekly HD in outpatient DaVita dialysis centres between 2004 and 2016. Patients with at least 5 years of follow-up since the initiation of HD or death within 5 years were included; 105 variables relating to demographics, HD treatment and laboratory measurements were evaluated as predictors of 5-year mortality utilizing a machine learning approach (random forest). RESULTS: A total of 363 patients were included in the analysis, with 84 patients having started HD at <12 years of age. Low albumin and elevated lactate dehydrogenase (LDH) were the two most important predictors of 5-year mortality. Other predictors included elevated red blood cell distribution width or blood pressure and decreased red blood cell count, haemoglobin, albumin:globulin ratio, ultrafiltration rate, z-score weight for age or single-pool Kt/V (below target). Mortality was predicted with an accuracy of 81%. CONCLUSIONS: Mortality in paediatric and young adult patients on chronic HD is associated with multifactorial markers of nutrition, inflammation, anaemia and dialysis dose. This highlights the importance of multimodal intervention strategies besides adequate HD treatment as determined by Kt/V alone. The association with elevated LDH was not previously reported and may indicate the relevance of blood-membrane interactions, organ malperfusion or haematologic and metabolic changes during maintenance HD in this population.

Hemodialysis (HD) dose and ultrafiltration rate are associated with survival in pediatric and adolescent patients on chronic HD-a large observational study with follow-up to young adult age.

BACKGROUND: Hemodialysis (HD) dose targets and ultrafiltration rate (UFR) limits for pediatric patients on chronic HD are not known and are derived from adults (spKt/V>1.4 and <13 ml/kg/h). We aimed to characterize how delivered HD dose and UFR are associated with survival in a large cohort of patients who started HD in childhood. METHODS: Retrospective analysis on a cohort of patients <30 years, on chronic HD since childhood (<19 years), having received thrice-weekly HD 2004-2016 in outpatient DaVita centers. OUTCOME: Survival while remaining on HD. PREDICTORS: (I) primary analysis: mean delivered dialysis dose stratified as spKt/V ≤1.4/1.4-1.6/>1.6 (Kaplan-Meier analysis), (II) secondary analyses: UFR and alternative dialysis adequacy measures [eKt/V, body-surface normalized Kt/BSA] on continuous scale (Weibull regression model). RESULTS: A total of 1780 patients were included (age at the start of HD: 0-12y: n=321, >12-18y: n=1459; median spKt/V=1.55, eKt/V=1.31, Kt/BSA=31.2 L/m2, UFR=10.6 mL/kg/h). (I) spKt/V<1.4 was associated with lower survival compared to spKt/V>1.4-1.6 (P<0.001, log-rank test), and spKt/V>1.6 (P<0.001), with 10-year survival of 69.3% (59.4-80.9%) versus 83.0% (76.8-89.8%) and 84.0% (79.6-88.5%), respectively. (II) Kt/BSA was a better predictor of survival than spKt/V or eKt/V. UFR was additionally associated with survival (P<0.001), with increased mortality <10/>18 mL/kg/h. Associations did not alter significantly following adjustment for demographic characteristics (age, etiology of kidney disease, and ethnicity). CONCLUSIONS: Our results suggest usefulness of targeting Kt/BSA>30 L/m2 for best long-term outcomes, corresponding to spKt/V>1.4 (>12 years) and >1.6 (<12 years). In contrast to adults, higher UFR of 10-18 ml/kg/h was not associated with greater mortality in this population.

Conversion to permanent vascular access is associated with improved markers of hemodialysis efficacy in children: Pediatric nephrology research consortium study.

BACKGROUND AND OBJECTIVES: Arteriovenous fistulae (AVF) and grafts (AVG) are preferred permanent vascular access (PVA) for chronic hemodialysis (HD) patients. Our objective was to examine the change in markers of HD efficacy after successful establishment of a PVA among children who started HD with a tunneled cuffed catheter (TCC). MATERIALS AND METHODS: Retrospective chart reviews were completed on patients from 20 pediatric dialysis centers. All patients used TCC prior to AVF/AVG, and each patient acted as his/her own control. Data on markers of HD efficacy (single-pool Kt/V, urea reduction ratio (URR), serum albumin and hematocrit (Hct)) were collected at the creation of AVF/AVG and for 2 years thereafter. Statistical methods included hypothesis testing and statistical modeling after adjusting for relevant demographic variables. RESULTS: First PVA was created in 98 individual children: 87 (89%) were AVF and 11 (11%) were AVG. The mean TCC vintage prior to AVF/AVG was 10.4 ± 17.3 months. At 1-year follow-up, Kt/V improved by 0.15 ± 0.06 (p = 0.02) and URR improved by 4.54 ± 1.17% (p < 0.0001). Furthermore, PVA was associated with improved serum albumin by 0.31 ± 0.07 g/dL (p < 0.0001) and Hct by 2.80 ± 0.65% (p < 0.0001) at 1 year. These HD efficacy markers remained statistically significant at 2nd-year follow-up. These observations were further supported by the adjusted models. Conversion to AVF was associated with statistically significant improvement in all four markers of HD efficacy at 1-year follow-up. This trend was not demonstrated for subjects who were converted to AVG. CONCLUSION: Switching to PVA was associated with improved markers of HD efficacy, single-pool Kt/V, URR, serum albumin, and Hct. This improvement was mostly demonstrated at 1 year and maintained for the 2nd year. The potential differential impact of the type of PVA on the trajectory of markers of HD efficacy should be further investigated.

Tunneled hemodialysis catheter care practices and blood stream infection rate in children: results from the SCOPE collaborative.

OBJECTIVE: The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) collaborative seeks to reduce hemodialysis (HD) catheter-associated blood stream infections (CA-BSI) by increasing implementation of standardized HD catheter care bundles. We report HD catheter care practices and HD CA-BSI rates from SCOPE. METHODS: Catheter care practices and infection events were collected prospectively during the study period, from collaborative implementation in June 2013 through May 2017. For comparative purposes, historical data, including patient demographics and HD CA-BSI events, were collected from the 12 months prior to implementation. Catheter care bundle compliance in 5 care bundle categories was monitored across the post-implementation reporting period at each center via monthly care observation forms. CA-BSI rates were calculated monthly, and reported as number of infections per 100 patient months. Changes in CA-BSI rates were assessed using generalized linear mixed model (GLMM) techniques. RESULTS: Three hundred twenty-five patients with tunneled HD catheters [median (IQR) age 12 years (6, 16), M 53%, F 47%] at 15 centers were included. A total of 3996 catheter care observations over 4170 patient months were submitted with a median (IQR) 5 (2, 14) observations per patient. Overall bundle compliance was high at 87.6%, with a significant and progressive increase (p < 0.001) in compliance for 4/5 bundle categories over the 48-month study period. The adjusted CA-BSI rate significantly decreased over time from 3.3/100 patient months prior to implementation of the care bundles to 0.8/100 patient months 48 months after care bundle implementation (p < 0.001). CONCLUSIONS: Using quality improvement methodology, SCOPE has demonstrated a significant increase in compliance with a majority of HD catheter care practices and a significant reduction in the rate of CA-BSI among children maintained on HD.

Predictors of time to first cannulation for arteriovenous fistula in pediatric hemodialysis patients: Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Permanent vascular access (PVA) is preferred for long-term hemodialysis. Arteriovenous fistulae (AVF) have the best patency and the lowest complication rates compared to arteriovenous grafts (AVG) and tunneled cuffed catheters (TCC). However, AVF need time to mature. This study aimed to investigate predictors of time to first cannulation for AVF in pediatric hemodialysis patients. METHODS: Data on first AVF and AVG of patients at 20 pediatric dialysis centers were collected retrospectively, including demographics, clinical information, dialysis markers, and surgical data. Statistical modeling was used to investigate predictors of outcome. RESULTS: First PVA was created in 117 children: 103 (88%) AVF and 14 (12%) AVG. Mean age at AVF creation was 15.0 ± 3.3 years. AVF successfully matured in 89 children (86.4%), and mean time to first cannulation was 3.6 ± 2.5 months. In a multivariable regression model, study center, age, duration of non-permanent vascular access (NPVA), and Kt/V at AVF creation predicted time to first cannulation, with study center as the strongest predictor (p < 0.01). Time to first cannulation decreased with increasing age (p = 0.03) and with increasing Kt/V (p = 0.01), and increased with duration of NPVA (p = 0.03). Secondary failure occurred in 10 AVF (11.8%). Time to first cannulation did not predict secondary failure (p = 0.29), but longer time to first cannulation tended towards longer secondary patency (p = 0.06). CONCLUSIONS: Study center is the strongest predictor of time to first cannulation for AVF and deserves further investigation. Time to first cannulation is significantly shorter in older children, with more efficient dialysis treatments, and increases with longer NPVA duration.

Understanding the Effects of Kidney Disease and Dialysis Treatment on Pharmacotherapy in Children.

Chronic kidney disease (CKD) and acute kidney injury (AKI) requiring renal replacement therapy (RRT) by dialysis are rare conditions in pediatric patients. In pediatric patients with CKD, dialysis is mainly performed using peritoneal dialysis (PD) or intermittent hemodialysis (HD). In patients with AKI, continuous renal replacement therapy (CRRT) using hemofiltration, hemodialysis, or both techniques can be used. This chapter reviews (1) physiology and epidemiology of kidney disease and dialysis in children and (2) pharmacokinetic principles to be considered for developing pediatric dose recommendations under different dialysis modalities. Methods for both calculating and predicting dialysis drug clearance are reviewed; scaling approaches for predicting dialysis clearance in pediatric patients from data obtained in adults are discussed.

Age- and weight-based differences in haemodialysis prescription and delivery in children, adolescents and young adults.

Background: Limited systematic data are available on prescription and dosing of haemodialysis (HD) in children and adolescents compared with adults. We aimed to characterize age- and weight-based differences in HD delivery in children, adolescents and young adults. Methods: This is a retrospective observational study including 1852 patients <30 years on chronic HD from childhood (53 903 HD sessions), receiving thrice weekly outpatient HD between 2004 and 2016 in the USA (6075 patient-years, of which 2535 were in patients aged 1-18 years; weight range 8.3-168 kg). Median individual prescriptions per year were calculated and overall 50% (IQR) and 90% distribution ranges over age and weight were derived. Repeated measurements analysis of variance assessed differences between age and weight groups. Results: Prescriptions significantly differed among age and weight groups (P < 0.001). Lower weight patients (<75 kg) had higher (inter-quartile range, IQR) weight-normalized blood flow rate (highest in <25 kg: QB/kg = 6.5-9.1 mL/min/kg), urea dialytic clearance (KD/kg) and single pool Kt/V (spKt/V) (<25 kg: 1.43-1.78; 25-50 kg: 1.52-1.92; 50-75 kg: 1.43-1.74) than heavier patients (lowest in >100 kg: QB/kg = 3.1-4.0 mL/min/kg, spKt/V = 1.22-1.47, respectively). Adolescents had significantly lower QB/kg, KD/kg and spKt/V (1.34-1.71) compared with adults (1.45-1.79) and children <12 years (range of 25th percentiles: 1.37-1.44). Dialytic clearance derived from a mechanistic equation underpredicted KD in children but not in young adults. Significant growth retardation was observed, with the proportion of patients <3rd percentile (height for age) decreasing from 71% (1-2 years) to 15% (>18 years). Conclusion: Delivered HD treatment varies with age and weight and is more intensified in children aged <12 years, compared with adolescents and overweight young adults, who appear to be at highest risk of receiving suboptimal treatment. Still, delivery of target or higher spKt/V values did not result in appropriate growth in these children, questioning the value of spKt/V as a measure of HD adequacy in children. Provided ranges of outpatient HD prescription can help clinicians and researchers in personalizing and optimizing delivery of dialysis treatment.

Approach to the treatment of the infant with hyponatremia.

Hyponatremia is an electrolyte abnormality that occurs in infancy due to a variety of inherited and acquired disorders. Infants with hyponatremia can present with neurologic symptoms such as vomiting, weakness, and seizures. Common causes of hyponatremia in the infant population are excess ingestion or administration of hypotonic fluids and excessive gastrointestinal salt loss. Hyponatremia in infancy also can be a sign of less common disorders, such as mineralocorticoid deficiency or resistance, and disregulation of arginine vasopressin with impaired free-water removal. Treatment of infants with hyponatremia is dependent on the severity of symptoms and the cause of hyponatremia. In nephrogenic syndrome of inappropriate antidiuresis (NSIAD), fluid retention is due to a gain-of-function mutation in the arginine vasopressin receptor 2 (AVPR2) gene leading to low arginine vasopressin levels. We describe the case of an infant with hyponatremia due to NSIAD, whose mother also has a known mutation in the AVPR2 gene. We report the approach to the treatment of hyponatremia and its unique challenges in infancy.

Intradialytic Hypotension and Mortality in Adolescents and Young Adults With Kidney Failure Receiving Maintenance Hemodialysis.

Rationale & Objective: Intradialytic hypotension (IDH) is associated with mortality in adults with kidney failure requiring hemodialysis (HD); however, large-scale pediatric studies are lacking. Moreover, there is no evidence-based consensus definition of IDH in pediatric literature. We aimed to examine the association of commonly used definitions of IDH with mortality in adolescents and young adults. Study Design: This was a retrospective observational cohort study. Setting & Participants: In total, 1,199 adolescents and young adults (N = 320, aged 10-18 years and N = 879, aged 19-21 years) who initiated HD in a large dialysis organization were included. Exposures: This study used different definitions of IDH. Outcome: The study outcome was 2-year all-cause mortality. Analytical Approach: Several definitions of IDH were selected a priori based on a literature review. Patients were classified as having IDH if it was present in at least 30% of HD treatments during the first 90 days after dialysis initiation. Cox proportional hazards regression was used to test whether IDH associated with 2-year all-cause mortality. Results: Over a 2-year follow-up period, 54 (4.5%) patients died. Dependent on its definition, IDH was present in 2.9%-61.1% of patients. After the multivariable adjustment for sociodemographic and clinical characteristics, we found no association of IDH with mortality. Results were consistent across subgroups stratified by age (aged <18 and 19-21 years) and predialysis systolic blood pressure (<120, 120-150, and >150 mm Hg). We also examined IDH as occurring in <5%, 5%-29%, 30%-50%, and >50% of baseline treatments, and did not find a dose-response association with mortality (P > 0.05). Limitations: Owing to low event rates, our current sample size may have been too small to detect a difference in mortality. Conclusions: Our study found that IDH was not associated with mortality in adolescents and young adults.

Intradialytic hypotension (IDH), or hypotension experienced during dialysis, is common among children and young adults with kidney failure requiring hemodialysis. We examined the association of commonly used definitions of IDH with death in adolescents and young adults with kidney failure receiving hemodialysis. Intradialytic hypotension was present in 2.9%-61.1% of patients, depending on the definition, and over a 2-year follow-up period, 4.5% of the patients died. We found no association of IDH with mortality.

Cystatin C in children on chronic hemodialysis.

BACKGROUND: Cystatin C (CyC) concentration has been suggested as a marker of middle-molecule accumulation, hemodialysis (HD) adequacy and for estimating residual renal function (RRF), but it has not been studied in pediatric HD. High CyC is associated with increased cardiovascular disease (CVD). We investigated CyC kinetics and the effect of RRF on CyC in a pediatric HD population. METHODS: A total of 21 HD sessions and 20 interdialytic periods were analyzed in seven patients, age 5-19 years, of whom four were anuric (A) and three were non-anuric (NA). CyC was measured before (preHD) and after (postHD) three standard HD sessions in 1 week and prior to the first session of the following week. RESULTS: We found no difference (p=0.67) in CyC concentration between preHD CyC (9.85 ± 2.15 mg/l; A vs. NA, p=0.37) and postHD CyC (10.04 ± 2.83 mg/l; A vs NA, p=0.28). The weekly average preHD CyC median concentration was 10.14 mg/l (A vs. NA, p=0.87) and correlated with age (r=0.808, p=0.03) and height measurement (r=0.799, p=0.03), but not with RRF, single-pool Kt/V, ultrafiltration, HD duration or blood liters processed. CONCLUSIONS: Cystatin C is very elevated in children on HD. It does not rise between HD sessions, is not removed by standard HD and remains at steady state; therefore, elimination is extrarenal. Low RRF does not affect CyC elimination. CyC increases with age and height. If a high CyC concentration can be proven to have a causative role in the development of CVD, routine intensified HD regimens in children may be indicated for its removal.

Persistent Increase in Serum Ferritin Levels despite Converting to Permanent Vascular Access in Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study.

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = 0.049) and baseline serum ferritin level (p = 0.017). Increasing serum ferritin after conversion to PVA is concerning. This increase is not associated with serum hematocrit trends. Future studies should investigate the correlation of serum transferrin saturation and ferritin levels in pediatric HD patients.

Vascular involvement in tuberous sclerosis.

Vascular involvement in tuberous sclerosis (TS) is rare. Central and peripheral aneurysms and large and medium size arterial stenotic-occlusive disease have been reported in patients with TS. We present here three pediatric patients with TS and severe vascular abnormalities, followed by a review of the literature. The three cases include a 14-month-old girl with polycystic kidneys and cerebral tubers who had a large asymptomatic abdominal aortic aneurysm, a 2-year-old boy with multiple features of TS who had hypertension and was found to have mid-aortic syndrome with bilateral renal artery stenosis, and an 18-year-old girl with abdominal pain and TS features who had greater than 70% celiac artery stenosis. In all cases, noninvasive vascular imaging modalities were utilized for either initial diagnosis, surveillance, or both. These cases highlight the collaborative roles of the pediatric nephrologist and cardiovascular imager in the diagnosis and management of the vascular complications in TS patients. Appropriate care can only be made through a high index of suspicion.

Understanding Urea Kinetic Factors That Enhance Personalized Hemodialysis Prescription in Children.

Urea dialyzer clearance (KD) has been suggested to be underpredicted from blood flow (QB), dialysate flow (QD), and in vitro mass transfer-area coefficient of urea (KoA) in pediatric hemodialysis (HD) patients using a widely accepted mechanistic equation. We characterize factors that could explain this, assuming that it results from a bias between reported in vitro and actual in vivo KoA. An adult urea kinetic model was scaled to 923 patients aged 1-29 years based on pediatric physiologic knowledge (intercompartmental clearance, volumes of distribution). Using data from 2,676 HD sessions of those patients (pre-/post-HD urea concentrations and HD treatment parameters), mixed effect modeling was applied to estimate individual KoA correction factors (fKoA) required for unbiased KD and post-HD urea concentration predictions in vivo. QD/QB ratio was most strongly associated with individual fKoA estimates (P < 0.001; fKoA = -1%, 18%, and 110% at QD/QB ratios of 1.5, 2, and 5). Additional factors included in the model were filter flux (-12% lower fKoA for low- vs high-flux filters), ultra-filtration rate, and true QB (lower than nominal QB ≥200 ml/min). Of note, high QD/QB ratios used in children ≤6 years were associated with significant underprediction of KD in vivo, with post-HD urea concentrations being 23% lower than expected. In conclusion, dialyzers should be characterized under pediatric conditions where high QD/QB ratios are used. Our model can be used to prevent underestimation of urea clearance, allowing shorter dialysis sessions, higher quality of life, and individualized treatment prescription in children on maintenance HD.

A Rare and Extreme Case of Vulvar Swelling in the Setting of Nephrotic Syndrome in a Prepubertal Girl.

BACKGROUND: We present a rare case of severe vulvar edema secondary to steroid-refractory nephrotic syndrome in a prepubertal girl. CASE: The patient is an 8-year-old girl who presented during nephrotic syndrome relapse. She exhibited severe mons pubis and labial edema. She was treated with local symptomatic measures such as sitz baths, barrier ointment, and labial sling, with minimal relief. Improvement ultimately occurred after bilateral nephrectomy. SUMMARY AND CONCLUSION: Vulvar edema is rare in prepubertal girls. In this case, the edema was secondary to steroid-refractory nephrotic syndrome and was not responsive to local treatment measures. There is a paucity of data on effective treatment of vulvar edema in young girls. Our goal is to raise awareness of such pathology, which might lead to development of uniform guidelines for treatment of this condition.

Glucose control by the kidney: an emerging target in diabetes.

The full significance of the kidney's role in glucose homeostasis is now well recognized. For example, it is now known that renal gluconeogenesis contributes substantially to total-body glucose release in the postabsorptive state. The kidney contributes to glucose homeostasis by filtering and reabsorbing glucose. Under normal circumstances, glucose filtered by glomeruli is completely reabsorbed, but glucosuria may occur under conditions of hyperglycemia or reduced reabsorptive capacity. The sodium-glucose cotransporter SGLT2 (encoded by the SLC5A2 gene), which is expressed almost exclusively in proximal tubules, mediates approximately 90% of active renal glucose reabsorption. This transporter can be blocked by SGLT2 inhibitors, a class of compound that may prove effective in managing type 2 diabetes. The glucosuria induced by these compounds has a naturally occurring parallel in familial renal glucosuria (FRG), a condition in which SGLT2 mutations reduce renal reabsorptive capacity. Interestingly, the chronic glucosuria of patients with FRG does not appear to be associated with other pathological changes, and patients with FRG are mostly asymptomatic. This suggests that glucosuria is not intrinsically detrimental. Selective SGLT2 inhibitors are currently in clinical trials.