Faculty Bibliography

BACKGROUND: Patients with nephrolithiasis and hyperoxaluria generally are advised to follow a low-oxalate diet. However, most people do not eat isolated nutrients, but meals consisting of a variety of foods with complex combinations of nutrients. A more rational approach to nephrolithiasis prevention would be to base dietary advice on the cumulative effects of foods and different dietary patterns rather than single nutrients. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: Recurrent stone formers with hyperoxaluria (urine oxalate > 40mg/d). INTERVENTION: The intervention group was asked to follow a calorie-controlled Dietary Approaches to Stop Hypertension (DASH)-style diet (a diet high in fruit, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, sweets, and meat), whereas the control group was prescribed a low-oxalate diet. Study length was 8 weeks. OUTCOMES: Primary: change in urinary calcium oxalate supersaturation. SECONDARY: Changes in 24-hour urinary composition. RESULTS: 57 participants were randomly assigned (DASH group, 29; low-oxalate group, 28). 41 participants completed the trial (DASH group, 21; low-oxalate group, 20). As-treated analysis showed a trend for urinary oxalate excretion to increase in the DASH versus the low-oxalate group (point estimate of difference, 9.0mg/d; 95% CI, -1.1 to 19.1mg/d; P=0.08). However, there was a trend for calcium oxalate supersaturation to decrease in the DASH versus the low-oxalate group (point estimate of difference, -1.24; 95% CI, -2.80 to 0.32; P=0.08) in association with an increase in magnesium and citrate excretion and urine pH in the DASH versus low-oxalate group. LIMITATIONS: Limited sample size, as-treated analysis, nonsignificant results. CONCLUSIONS: The DASH diet might be an effective alternative to the low-oxalate diet in reducing calcium oxalate supersaturation and should be studied more.

Context. Ingestion of glyphosate-surfactant herbicides (GlySH) can result in acute kidney injury, electrolyte abnormalities, acidosis, cardiovascular collapse, and death. In severe toxicity, the use of hemodialysis is reported, but largely unsupported by kinetic analysis. We report the dialysis clearance of glyphosate following a suicidal ingestion of a glyphosate-containing herbicide. Case details. A 62-year-old man was brought to the emergency department (ED) 8.5 h after drinking a bottle of commercial herbicide containing a 41% solution of glyphosate isopropylamine, in polyoxyethyleneamine (POEA) surfactant and water. He was bradycardic and obtunded with respiratory depression necessitating intubation and mechanical ventilation. Initial laboratory results were significant for the following: pH, 7.11; PCO2, 64 mmHg; PO2, 48 mmHg; potassium, 7.8 mEq/L; Cr 3.3, mg/dL; bicarbonate, 22 mEq/L; anion gap, 18 mEq/L; and lactate, 7.5 mmol/L. Acidosis and hyperkalemia persisted despite ventilation and fluid resuscitation. The patient underwent hemodialysis 16 h post ingestion, after which he demonstrated resolution of acidosis and hyperkalemia, and improvement in clinical status. Serum glyphosate concentrations were drawn prior to, during, and after hemodialysis. The extraction ratio and hemodialysis clearance were calculated to be 91.8% and 97.5 mL/min, respectively. Discussion. We demonstrate the successful clearance of glyphosate using hemodialysis, with corresponding clinical improvement in a patient with several poor prognostic factors (advanced age, large volume ingested, and impaired consciousness). The effects of hemodialysis on the surfactant compound are unknown. Hemodialysis can be considered when severe acidosis and acute kidney injury complicate ingestion of glyphosate-containing products.

Cystinuria is a genetic cause of recurrent kidney stones which may be more recurrent and larger than more common non-cystine stones. They may have a greater impact on health-related quality of life (HRQoL). We measured this impact by surveying HRQoL in patients with stones, comparing non-cystine stone formers (NCSF) to cystine stone formers (CYSF) and both groups to normative values of the US population. We used SF-36v2 via an internet instrument. CYSF patients were recruited via cystinuria-related websites, two patient advocacy groups, and an active endourology practice. NCSF patients were recruited from the same practice and by email. Total n surveyed with scorable data: 214 CYSF and 81 NCSF. The participants included 128 men and 161 women. The group of CYSF were significantly younger (39 vs. 54 years) and suffered longer from kidney stones (255 vs. 136 months). CYSF patients had significantly more episodes of stones than NCSF patients in the last year (N = 108 CYSF, N = 20 NCSF). More frequent stones in the last year and mental comorbidities most often predicted worse scores in the individual HRQoL domains. However, cystine stone composition was a significant predictor of worse scores only for role emotional. Better scores in all SF-36 domains were associated with greater time since the last kidney stone event. Although kidney stones are often transient, kidney stone formers, regardless of stone composition, have a worse HRQoL than the standard US population, which has a normative score of 50, such as general health (41.2 +/- 12.8), bodily pain (46.5 +/- 11.8) and mental health (45.1 +/- 12.6). CYSF are more frequent and severe stone formers compared with NCSF with a resulting greater, direct impact on the HRQoL of CYSF patients. Whether preventive strategies for cystinuria are being properly utilized by practitioners, and which strategies are most effective, should be established.

There is emerging evidence that mild chronic hyponatremia (MCH), highly prevalent in the elderly and once considered asymptomatic, is a major independent risk factor for falls, fall-related fractures (independent of osteoporosis, age, and sex), impaired attention and gait, reductions in bone mineral density (BMD), and even death. Although research on MCH and bone health is emerging and ongoing, it has not been recognized in orthopedics. Orthopedic surgeons must be educated regarding the impact of hyponatremia on bone, as osteoporotic fractures have enormous socioeconomic consequences, and the problem will worsen. Orthopedic surgeons should also be included in research, in education, and in the establishment of diagnostic and treatment protocols. In this article, we review the current concepts of MCH and its impacts on the skeletal system.

Introduction. Minimal Change Disease (MCD) is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

Tubulocystic renal cell carcinoma (TC-RCC) is a rare renal tumor composed of well-differentiated tubules and cysts lined by neoplastic cells with eosinophilic cytoplasm and prominent nucleoli. The origin of the tumor cells is still controversial. TC-RCC typically arises unilaterally. Involvement of both kidneys by multifocal TC-RCC has not been reported. In this study we report the first case of bilateral and multifocal TC-RCC. Immunohistochemical, cytogenetic and ultrastructural studies suggest TC-RCC is closely related to papillary RCC.

The recent trend to early initiation of dialysis (at eGFR >10 ml/min/1.73 m(2) ) appears to have been based on conventional wisdoms that are not supported by evidence. Observational studies using administrative databases report worse comorbidity-adjusted dialysis survival with early dialysis initiation. Although some have concluded that the IDEAL randomized controlled trial of dialysis start provided evidence that patients become symptomatic with late dialysis start, there is no definitive support for this view. The potential harms of early start of dialysis, including the loss of residual renal function (RRF), have been well documented. The rate of RRF loss (renal function trajectory) is an important consideration for the timing of the dialysis initiation decision. Patients with low glomerular filtration rate (GFR) may have sufficient RRF to be maintained off dialysis for years. Delay of dialysis start until a working arterio-venous access is in place seems prudent in light of the lack of harm and possible benefit of late dialysis initiation. Prescribing frequent hemodialysis is not recommended when dialysis is initiated early. The benefits of early initiation of chronic dialysis after episodes of congestive heart failure or acute kidney injury require further study. There are no data to show that early start benefits diabetics or other patient groups. Preemptive start of dialysis in noncompliant patients may be necessary to avoid complications. The decision to initiate dialysis requires informed patient consent and a joint decision by the patient and dialysis provider. Possible talking points for obtaining informed consent are provided.

Chronic kidney disease (CKD) is an important clinical co-morbidity that increases the risk of death and myocardial infarction in patients with coronary artery disease (CAD) even when treated with guideline-directed therapies. It is unknown, however, whether CKD influences the effects of CAD treatments on patients' health status, their symptoms, function, and quality of life. We performed a post hoc analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study to compare health status in patients with stable CAD with and without CKD defined as a glomerular filtration rate of <60 ml/min/1.73 m(2) randomized to either percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) or OMT alone. Health status was measured at baseline, 1, 3, 6, 12, 24, and 36 months of follow-up with the Seattle Angina Questionnaire in 310 patients with CKD and 1,719 patients without CKD. Linear mixed-effects models were used to analyze Seattle Angina Questionnaire scores longitudinally. Mean scores for angina-related quality of life, angina frequency, and physical limitation domains improved from baseline values in both patients with and without CKD and plateaued. Early improvement (1 to 6 months) was more common in patients treated with PCI plus OMT than with OMT alone in both patients with and without CKD. Treatment satisfaction scores were high at baseline in all groups and did not change significantly over time. In conclusion, although CKD is an important determinant of event-free survival in patients with stable CAD, it neither precludes satisfactory treatment of angina with PCI plus OMT or OMT alone nor is it associated with an unsatisfactory quality of life.

Introduction & Objectives: Genetic disorders are among the causes of the most severe stone disease. Among them, primary hyperoxaluria (PH), cystinuria, APRT deficiency, and Dent disease can also be associated with loss of kidney function. Due to their rarity, however, understanding of the impact of these stone diseases on kidney function over time is limited. We performed a cross-sectional study of kidney function in patients with each of these disorders over a range of ages. Material & Methods: Voluntary observational registries of the Rare Kidney Stone Consortium were queried. 155 patients with PH, 53 with cystinuria, 34 with APRT deficiency, and 78 with Dent disease had serum creatinine values available prior to development of end stage kidney failure. Serum creatinine at first presentation was used for calculation of eGFR. Kidney function was calculated by MDRD equation in adults and Schwartz equation in children. Spline curve was used to check linearity of plots. Results were compared with normal eGFR of 116 at 20 years of age with decline of 7.5 ml/min/1.73m2BSA per decade after age 30 years (Lindeman J Am Ger Soc, 1985). Results: Age at eGFR was 16.1+/-17.4, 39.8+/-16.7, 25.9+/-19.1, and 12.4+/-10.0 years (mean+/- SD) and the number of stones at presentation was 4.2+/-10.0, 1.9+/-1.8, 1.7+/-4.8, and 3.1+/-3.9 (mean+/-SD) in PH, cystinuria, APRT deficiency, and Dent patients, respectively. eGFR was 91.5, 80.2, 69.8, and 91.5 ml/min/1.73m2BSA in PH, cystinuria, APRT deficiency, and Dent disease patients, respectively. The change in eGFR per decade was -15 (2.1) ml/min/1.73m2 BSA (SE) in PH, -12 (2.2) in cystinuria, -16 (3.9) in APRT deficiency, and -26 (7.9) in Dent disease. Conclusions: Cross sectional data in patients with PH, cystinuria, APRT deficiency and Dent disease shows more rapid decline in kidney function by decade than observed in healthy subjects. Whether kidney damage is related to stone burden or to other factors remains to be determined. The distinction will be of importanc!