Faculty Bibliography

The 2012 KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for Anemia in Chronic Kidney Disease provides clinicians with comprehensive evidence-based recommendations to improve patient care. In this commentary, we review these recommendations and the underlying evidence. Most recommendations are well reasoned. For some, the evidence is unclear and recommendations require some qualification. While the KDIGO guideline stresses the potential risks of intravenous iron therapy, withholding iron might have its own risks. The recommendation to avoid hemoglobin levels falling below 9 g/dL sets a lower bound of "acceptability" that may increase blood transfusion. Given the lack of research supporting the optimal transfusion strategy for end-stage renal disease patients, it is difficult to weigh the risks and benefits of red blood cell transfusion. We find a paucity of evidence that hemoglobin concentration targeted between 11 and 11.5 g/dL is associated with a safety risk. Although the evidence that erythropoiesis-stimulating agent use improves patient quality of life is poor, it is possible that the instruments used to measure quality of life may not be well attuned to the needs of chronic kidney disease or dialysis patients. Our last section focuses specifically on the recommendations to treat anemia in children.

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.

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.

Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment, and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC, and PH, with an emphasis on childhood manifestations.

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!

PURPOSE OF REVIEW: Cystinuria is a rare genetic disease with increased urinary excretion of the poorly soluble amino acid cystine. It can lead to significant morbidity in affected patients due to the often large and recurrent resulting kidney stones. Treatment is focused on the prevention of stone formation. There have been few advances in the available therapeutic options for the disorder in the last 15-20 years. RECENT FINDINGS: Although no new treatments have emerged in the prevention of cystinuria in recent years, several developments hold promise for advancing the field of caring for affected patients. A new method of measuring urinary cystine and estimating potential for stone formation, called cystine capacity, may prove to be a useful tool in monitoring the disease. The discoveries of the mutations that cause cystinuria have led to a new classification system based on genotype that is more accurate than the prior phenotypic one. The finding of new compounds that inhibit cystine crystal growth in vitro, now being tested in animal models, may lead to new potential therapies in years to come. The Rare Kidney Stone Consortium has developed a registry and hopes to lead further efforts in dealing with cystinuria. SUMMARY: With several recent advances in the monitoring and treatment of cystinuria, and the gathering of clinical patient data, there are now opportunities for new management protocols and therapies.

PURPOSE: The combination of sepsis and ureteral calculus is a urological emergency. Traditional teaching advocates urgent decompression with nephrostomy tube or ureteral stent placement, although published outcomes validating this treatment are lacking. National practice patterns for such scenarios are currently undefined. Using a retrospective study design, we defined the surgical decompression rate in patients admitted to the hospital with severe infection and ureteral calculi. We determined whether a mortality benefit is associated with this intervention. MATERIALS AND METHODS: Patient demographics and hospital characteristics were extracted from the 2007 to 2009 Nationwide Inpatient Sample. We identified 1,712 patients with ureteral calculi and sepsis. Multivariate logistic regression was performed to determine the association between mortality and surgical decompression. RESULTS: Of the patients 78% underwent surgical decompression. Mortality was higher in those not treated with surgical decompression (19.2% vs 8.82%, p <0.001). Lack of surgical decompression was independently associated with an increased OR of mortality even when adjusting for patient demographics, comorbidities and geographic region of treatment (OR 2.6, 95% CI 1.9-3.7). CONCLUSIONS: Absent surgical decompression is associated with higher odds of mortality in patients with sepsis and ureteral calculi. Further research to determine predictors of surgical decompression is necessary to ensure that all patients have access to this life saving therapy.