Glycated Albumin and Adverse Clinical Outcomes in Patients With CKD: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Hemoglobin A1c (HbA1c) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,110 participants with CKD from the Chronic Renal Insufficiency Cohort study. EXPOSURE: Baseline GA levels. OUTCOME: Incident end-stage kidney disease (ESKD), cardiovascular disease (CVD) events, and all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: Participant characteristics included mean age 59.0±10.8 SD years; 1,357 (43.6%) female; and 1,550 (49.8%) with diabetes. The median GA was 18.7% (IQR, 15.8%-23.3%). During an average 7.9-year follow-up, there were 980 ESKD events, 968 CVD events, and 1,084 deaths. Higher GA levels were associated with greater risks of all outcomes, regardless of diabetes status: hazard ratios for ESKD, CVD, and death among participants with the highest quartile compared with quartile 2 (reference) were 1.42 (95% CI, 1.19-1.69), 1.67 (95% CI, 1.39-2.01), and 1.63 (95% CI, 1.37-1.94), respectively. The associations with CVD and death appeared J-shaped, with increased risk also seen at the lowest GA levels. Among patients with coexisting CKD and diabetes, the associations of GA with outcomes remained significant even after adjusting for HbA1c. For each outcome, we observed a significant increase in the fraction of new prognostic information when both GA and HbA1c were added to models. LIMITATIONS: Lack of longitudinal GA measurements; and HbA1c measurements were largely unavailable in participants without diabetes. CONCLUSIONS: Among patients with CKD, GA levels were independently associated with risks of ESKD, CVD, and mortality, regardless of diabetes status. GA added prognostic value to HbA1c among patients with coexisting CKD and diabetes. PLAIN-LANGUAGE SUMMARY: Hemoglobin A1c (HbA1c) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. In this cohort study of 3,110 individuals with non-dialysis-dependent CKD, GA levels were independently associated with risks of end-stage kidney disease, cardiovascular disease (CVD), and mortality. The associations with CVD and mortality appeared to be J-shaped. Among patients with coexisting CKD and diabetes, GA added prognostic value to HbA1c. Thus, GA may be a valuable complementary test to HbA1c in patients with CKD.

Nephrogenic Calciphylaxis Arising after Bariatric Surgery: A Case Series.

Nephrogenic calciphylaxis is associated with multiple risk factors including long-term dialysis dependence, hyperphosphatemia, hypercalcemia, parathyroid hormone derangements, vitamin K deficiency, obesity, diabetes mellitus, warfarin use, and female sex. Bariatric surgery is known to cause altered absorption, leading to mineral and hormonal abnormalities in addition to nutritional deficiency. Prior case reports on calciphylaxis development following bariatric surgery have been published, though are limited in number. We report a case series of five bariatric patients from a single institution who developed nephrogenic calciphylaxis between 2012 and 2018. These patients had a history of bariatric surgery, and at the time of calciphylaxis diagnosis, demonstrated laboratory abnormalities associated with surgery including hypercalcemia (n = 3), hyperparathyroidism (n = 2), hypoalbuminemia (n = 5), and vitamin D deficiency (n = 5), in addition to other medication exposures such as vitamin D supplementation (n = 2), calcium supplementation (n = 4), warfarin (n = 2), and intravenous iron (n = 1). Despite the multifactorial etiology of calciphylaxis and the many risk factors present in the subjects of this case series, we submit that bariatric surgery represents an additional potential risk factor for calciphylaxis directly stemming from the adverse impact of malabsorption and overuse of therapeutic supplementation. We draw attention to this phenomenon to encourage early consideration of calciphylaxis in the differential for painful skin lesions arising after bariatric surgery as swift intervention is essential for these high-risk patients.

Molecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification.

Cardiovascular disease is the most common cause of death worldwide, especially beyond the age of 65 years, with the vast majority of morbidity and mortality due to myocardial infarction and stroke. Vascular pathology stems from a combination of genetic risk, environmental factors, and the biologic changes associated with aging. The pathogenesis underlying the development of vascular aging, and vascular calcification with aging, in particular, is still not fully understood. Accumulating data suggests that genetic risk, likely compounded by epigenetic modifications, environmental factors, including diabetes and chronic kidney disease, and the plasticity of vascular smooth muscle cells to acquire an osteogenic phenotype are major determinants of age-associated vascular calcification. Understanding the molecular mechanisms underlying genetic and modifiable risk factors in regulating age-associated vascular pathology may inspire strategies to promote healthy vascular aging. This article summarizes current knowledge of concepts and mechanisms of age-associated vascular disease, with an emphasis on vascular calcification.

Assessment of diagnostic delay, morbidity, and mortality outcomes in 302 calciphylaxis patients over a 17-year period: A retrospective cohort study.

BACKGROUND: Calciphylaxis patients historically have experienced diagnostic challenges and high morbidity, however limited data is available examining these characteristics over time. OBJECTIVE: The primary goals were to a) investigate factors associated with diagnostic delay of calciphylaxis and b) assess morbidity outcomes. The secondary goal was to provide updated mortality rates. METHODS: A retrospective review of 302 adult patients diagnosed with calciphylaxis between January 1, 2006 and December 31, 2022 was conducted. Univariate and multivariate statistical analyses were performed. RESULTS: Non-nephrogenic calciphylaxis (p=0.0004) and involvement of the fingers (p=0.0001) were significantly associated with an increased diagnostic delay, whereas involvement of the arms (p=0.01) and genitalia (p=0.022) resulted in fewer days to diagnosis. Almost all patients with genitalia, finger, or toe involvement had nephrogenic disease. The number of complications per patient decreased with time, especially for wound infections (p=0.028), increase in lesion number (p=0.012), and recurrent hospitalizations (p=0.020). Updated 1-year mortality rates were 36.70% and 30.77% for nephrogenic and non-nephrogenic calciphylaxis, respectively. LIMITATIONS: Limitations include the retrospective nature and data from a single institution. CONCLUSION: Diagnostic delay, particularly in non-nephrogenic calciphylaxis, and complications per patient decreased with time, highlighting the importance of continued awareness to expedite diagnosis. Mortality rates have continued to improve in recent years.

Healthcare Resource Utilization and Goals of Care Discussions in Patients with Cirrhosis and Acute Kidney Injury.

BACKGROUND: Patients with cirrhosis and acute kidney injury (AKI) are critically ill and have high health care resource utilization (HCRU). The impact and timing of goals of care discussions on HCRU are not well described. METHODS: 221 patients enrolled in a prospective cohort study of patients admitted with AKI and cirrhosis were reviewed. Documentation and timing of a goals of care discussions were analyzed as predictors of HCRU, defined as a composite outcome of intubation, initiation of renal replacement therapy, and/or admission to the intensive care unit. RESULTS: Median MELD score was 26 [IQR 19, 33]. 29% patients were listed for liver transplant. 90-day mortality was 61%. 51% patients had at least one HCRU episode. Code status changed from admission to discharge from 91%/7%/0% to 68%/14%18% (full code/do not resuscitate/comfort measures, p < 0.001). 28% patients underwent goals of care discussions, with change in code status at a median of 16 [9, 22] days into admission. Only 18% of discussions were within 7 days of admission and all were after an HCRU event. Being listed for liver transplant was not associated with whether goals of care discussions occurred (23% listed vs. 31% non-listed, p = 0.24) but was associated with higher HCRU (69% vs. 43%; p < 0.001). CONCLUSION: Goals of care discussions occurred late into the hospital course, after episodes of HCRU. Efforts should be made to engage in these discussions earlier in the hospital stay, which may decrease HCRU rates in this critically ill population and align with patients' goals of care.

Intravenous sodium thiosulphate for vascular calcification of hemodialysis patients-a systematic review and meta-analysis.

BACKGROUND: Vascular calcification (VC) is a common comorbidity among patients with chronic kidney disease (CKD), indicating major cardiovascular events. This study aimed to evaluate the effects and safety of intravenous sodium thiosulphate (STS) for VC in CKD patients. METHODS: Electronic databases were searched for clinical trials that provided data comparing outcomes among patients treated with and without STS. The PRISMA guidelines were followed. Efficacy was assessed using calcification scores and arterial stiffness. Safety was examined by analyzing adverse symptoms, electrolytes and bone mineral density (BMD). Random-effects models were performed. Meta-regression and sensitivity analysis were done. The risk of bias was assessed using the Cochrane tools. RESULTS: Among the 5601 publications, 6 studies involving 305 participants (mean age: 56 years, male: 56.6%) with all participants on maintenance hemodialysis met eligibility criteria. For efficacy, the progression in Agatston scores in the coronary arteries [107 patients, mean difference (MD): -241.27, 95% confidence interval (95% CI): -421.50 to -61.03] and iliac arteries (55 patients, MD: -382.00, 95% CI: -751.07 to -12.93) was lower in the STS treated group compared with controls. The increase in pulse wave velocity was lower in the STS group (104 patients, MD: -1.29 m/s, 95% CI: -2.24 to -0.34 m/s). No association was found between the change in calcification scores and STS regimen. For safety, gastrointestinal symptoms (e.g. nausea) and increased anion gap acidosis were noted. No reduction in BMD by STS was observed. CONCLUSIONS: Intravenous STS may attenuate the progression of VC and arterial stiffness in hemodialysis patients. Large and well-designed randomized controlled trials are warranted.

Zoledronic Acid-Associated Fanconi Syndrome in Patients With Cancer.

Zoledronic acid (ZA) is an antiresorptive agent typically used for fracture prevention in postmenopausal osteoporosis, malignancy-associated metastatic bone lesions, and as a treatment for hypercalcemia. ZA is excreted almost entirely by the kidney; as a result, a reduction in renal clearance can lead to its accumulation and potential renal toxicity. Although uncommon, acute kidney injury (AKI) from intravenous bisphosphonates has been described, with different patterns including tubulointerstitial nephritis, acute tubular necrosis, as well as focal segmental glomerulosclerosis. Here we present 4 patients with an underlying malignancy who each developed evidence of generalized proximal tubular dysfunction, also known as Fanconi syndrome, approximately 1 week after receiving treatment with ZA. On presentation, all patients had AKI, low serum bicarbonate levels, abnormal urinary acidification, hypophosphatemia, hypokalemia, and increased urine amino acid excretion or renal glycosuria. Based on the temporal association between ZA infusion and the development of these electrolyte abnormalities, each case is highly suggestive of ZA-associated Fanconi syndrome. Due to the severity of presentation, all required discontinuation of ZA and ongoing electrolyte repletion. Nephrologists and oncologists should be aware of this complication and consider ZA as a possible trigger of new-onset Fanconi syndrome.

The association between olfactory and gustatory dysfunction and chronic kidney disease.

BACKGROUND: Olfactory and gustatory changes may contribute to poor appetite and food aversion in chronic kidney disease (CKD), though the prevalence of olfactory and gustatory dysfunction is not known in the CKD population. METHODS: We conducted a cross-sectional study among 3527 US adults aged ≥40 years old in the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2014. We measured the prevalence of olfactory and gustatory dysfunction among patients with CKD defined as eGFR < 60 ml/min/1.73m2 using the "scratch and sniff" NHANES Pocket Smell Test and quinine whole-mouth test. We also examined the association between CKD and olfactory/gustatory dysfunction, and nutritional markers. RESULTS: The prevalence of olfactory dysfunction was 30% among CKD and 15% among non-CKD (p < 0.001). The prevalence of gustatory dysfunction was 13% among CKD and 17% among non-CKD (p = 0.10). After adjusting for confounders, CKD was significantly associated with olfactory dysfunction (OR = 1.47, 95% CI [1.07, 2.01]; p = 0.02) but not gustatory dysfunction (OR = 1.76, 95%CI [0.99, 3.11]; p = 0.05). Among the CKD population, the odds of olfactory dysfunction was 72% higher for every 10 kg decrease in grip strength (OR = 1.72, 95% CI [1.39, 2.13]; adjusted p = 0.005). CONCLUSION: CKD was associated with higher odds of olfactory but not gustatory dysfunction. Olfactory dysfunction was associated with lower grip strength among those with CKD. Screening and early intervening on olfactory dysfunction among CKD may preserve muscle strength and improve nutritional status in this vulnerable population.

Penile calciphylaxis: A retrospective case-control study.

BACKGROUND: Calciphylaxis is a rare disorder characterized by skin necrosis caused by calcium deposition within vessels, thrombosis, and subsequent tissue ischemia. Penile involvement may rarely occur. OBJECTIVE: To identify risk factors, diagnosis, management, and mortality of patients with penile calciphylaxis. METHODS: A retrospective medical record review was conducted of 16 patients with penile calciphylaxis treated at 2 large urban tertiary care centers between January 2001 and December 2019. A control group of 44 male patients with nonpenile calciphylaxis at the same institution was included. RESULTS: The median survival of patients with penile calciphylaxis was 3.8 months (interquartile range, 27.0 months). Mortality was 50% at 3 months and 62.5% at 6 months for penile calciphylaxis, and 13.6% at 3 months and 29.5% at 6 months for controls (P = .008). Patients with penile calciphylaxis were less likely to be obese (P = .04) but more likely to have hyperparathyroidism (P = .0003) and end-stage renal disease (P = .049). LIMITATIONS: Retrospective study design and small sample size. CONCLUSIONS: This study further defines the disease course of penile calciphylaxis, which has high mortality. Imaging may be used to aid diagnosis. Risk factors include end-stage renal disease, hyperparathyroidism, and normal body mass index.

Clinical mimickers of calciphylaxis: A retrospective study.

BACKGROUND: Calciphylaxis is an ischemic vasculopathy with high morbidity and mortality. Early and accurate diagnosis is critical to management of calciphylaxis. Clinical mimickers may contribute to delayed or misdiagnosis. OBJECTIVE: To assess the rate and risk factors for misdiagnosis and to identify clinical mimickers of calciphylaxis. METHODS: A retrospective medical record review was conducted of patients with calciphylaxis at a large urban tertiary care hospital between 2006 and 2018. RESULTS: Of 119 patients diagnosed with calciphylaxis, 73.1% were initially misdiagnosed. Of patients not initially misdiagnosed, median time to diagnosis from initial presentation was 4.5 days (interquartile range, 1.0-23.3), compared to 33 days (interquartile range, 13.0-68.8) in patients who were initially misdiagnosed (P = .0002). The most common misdiagnoses were cellulitis (31.0%), unspecified skin infection (8.0%), and peripheral vascular disease (6.9%). Patients who were misdiagnosed frequently received at least 1 course of antibiotics. Patients with end-stage renal disease were less likely to be misdiagnosed than those without this disease (P = .001). LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: Understanding the risk factors for misdiagnosis of calciphylaxis is an opportunity for further education concerning this rare disease.

Assessment of outcomes of calciphylaxis.

BACKGROUND: Calciphylaxis is a rare thrombotic vasculopathy characterized by high morbidity and mortality. There is a paucity of studies examining longitudinal outcomes. OBJECTIVE: To assess mortality, days spent in the hospital, and amputations in patients with calciphylaxis. METHODS: A retrospective medical record review was conducted in 145 patients diagnosed with calciphylaxis at an urban tertiary care hospital from January 2006 to December 2018. RESULTS: Six-month mortality was 37.2%, and 1-year mortality was 44.1%. Patients with nephrogenic calciphylaxis had worse survival than those with nonnephrogenic calciphylaxis (P = .007). This difference in survival disappeared when limiting mortality to deaths due to calciphylaxis. Age (P = .003) and end-stage renal disease (P = .01) were risk factors associated with 1-year mortality. Diabetes mellitus was associated with greater total hospitalization days (coefficient, 1.1; 95% confidence interval, 1.01-1.4); bedside debridement was associated with fewer hospitalization days (coefficient, 0.8; 95% confidence interval, 0.7-0.9). Amputations were not associated with any of the examined risk factors. The use of warfarin followed by a transition to nonwarfarin anticoagulation was associated with decreased hazard of death (P = .01). LIMITATIONS: Retrospective nature. CONCLUSIONS: Calciphylaxis remains a complex, heterogeneous disease. Mortality is lower in patients with nonnephrogenic disease. These findings may be incorporated during discussions regarding the goals of care to facilitate informed shared decision making.

Kidney Function Decline among Black Patients with Sickle Cell Trait and Sickle Cell Disease: An Observational Cohort Study.

BACKGROUND: Sickle cell trait and sickle cell disease are thought to be independent risk factors for CKD, but the trajectory and predictors of kidney function decline in patients with these phenotypes are not well understood. METHODS: Our multicenter, observational study used registry data (collected January 2005 through June 2018) and included adult black patients with sickle cell trait or disease (exposures) or normal hemoglobin phenotype (reference) status (ascertained by electrophoresis) and at least 1 year of follow-up and three eGFR values. We used linear mixed models to evaluate the difference in the mean change in eGFR per year. RESULTS: We identified 1251 patients with sickle cell trait, 230 with sickle cell disease, and 8729 reference patients, with a median follow-up of 8 years. After adjustment, eGFR declined significantly faster in patients with sickle cell trait or sickle cell disease compared with reference patients; it also declined significantly faster in patients with sickle cell disease than in patients with sickle cell trait. Male sex, diabetes mellitus, and baseline eGFR ≥90 ml/min per 1.73 m2 were associated with faster eGFR decline for both phenotypes. In sickle cell trait, low hemoglobin S and elevated hemoglobin A were associated with faster eGFR decline, but elevated hemoglobins F and A2 were renoprotective. CONCLUSIONS: Sickle cell trait and disease are associated with faster eGFR decline in black patients, with faster decline in sickle cell disease. Low hemoglobin S was associated with faster eGFR decline in sickle cell trait but may be confounded by concurrent hemoglobinopathies. Prospective and mechanistic studies are needed to develop best practices to attenuate eGFR decline in such patients.

Serum Angiopoietin-2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis.

Acute kidney injury in decompensated cirrhosis has limited therapeutic options, and novel mechanistic targets are urgently needed. Angiopoietin-2 is a context-specific antagonist of Tie2, a receptor that signals vascular quiescence. Considering the prominence of vascular destabilization in decompensated cirrhosis, we evaluated Angiopoietin-2 to predict clinical outcomes. Serum Angiopoietin-2 was measured serially in a prospective cohort of hospitalized patients with decompensated cirrhosis and acute kidney injury. Clinical characteristics and outcomes were examined over a 90-day period and analyzed according to Angiopoietin-2 levels. Primary outcome was 90-day mortality. Our study included 191 inpatients (median Angiopoietin-2 level 18.2 [interquartile range 11.8, 26.5] ng/mL). Median Model for End-Stage Liver Disease (MELD) score was 23 [17, 30] and 90-day mortality was 41%. Increased Angiopoietin-2 levels were associated with increased mortality (died 21.9 [13.9, 30.3] ng/mL vs. alive 15.2 [9.8, 23.0] ng/mL; P < 0.001), higher Acute Kidney Injury Network stage (stage I 13.4 [9.8, 20.1] ng/mL vs. stage II 20.0 [14.1, 26.2] ng/mL vs. stage III 21.9 [13.0, 29.5] ng/mL; P = 0.002), and need for renal replacement therapy (16.5 [11.3, 23.6] ng/mL vs. 25.1 [13.3, 30.3] ng/mL; P = 0.005). The association between Angiopoietin-2 and mortality was significant in unadjusted and adjusted Cox regression models (P ≤ 0.001 for all models), and improved discrimination for mortality when added to MELD score (integrated discrimination increment 0.067; P = 0.001). Conclusion: Angiopoietin-2 was associated with mortality and other clinically relevant outcomes in a cohort of patients with decompensated cirrhosis with acute kidney injury. Further experimental study of Angiopoietin/Tie2 signaling is warranted to explore its potential mechanistic and therapeutic role in this population.

Mortality and Hospitalizations among Sickle Cell Disease Patients with End-Stage Kidney Disease Initiating Dialysis.

BACKGROUND: Sickle cell disease (SCD) is the most common inherited hematological disorder and a well-described risk factor for end-stage kidney disease (ESKD). Mortality and hospitalizations among patients with SCD who develop ESKD remain understudied. Furthermore, prior studies focused only on SCD patients where ESKD was caused by SCD. We aimed to describe mortality and hospitalization risk in all SCD patients initiating dialysis and explore risk factors for mortality and hospitalization. METHODS: We performed a national observational cohort study of African American ESKD patients initiating dialysis (2000-2014) in facilities affiliated with a large dialysis provider. SCD was identified by diagnosis codes and matched to a reference population (non-SCD) by age, sex, dialysis initiation year, and geographic region of care. Sensitivity analyses were conducted by restricting to patients where SCD was recorded as the cause of ESKD. RESULTS: We identified 504 SCD patients (mean age: 47 ± 14 years; 48% females) and 1,425 reference patients (mean age: 46 ± 14 years; 49% females). The median follow-up was 2.4 (IQR 1.0-4.5) years. Compared to the reference, SCD was associated with higher mortality risk (hazard ratio 1.66; 95% confidence interval [CI]: 1.36-2.03) and higher hospitalization rates (incidence rate ratio 2.12; 95% CI: 1.88-2.38) in multivariable analyses. Exploratory multivariable mortality risk models showed the largest mortality risk attenuation with the addition of time-varying hemoglobin and high-dose erythropoietin, but the association of SCD with mortality remained significant. Sensitivity analyses (restricted to ESKD caused by SCD) also showed significant associations between SCD and mortality and hospitalizations, but with larger effect estimates. High-dose erythropoietin was associated with the highest risk for mortality and hospitalization in SCD. CONCLUSIONS: Among ESKD patients, SCD is associated with a higher risk for mortality and hospitalization, particularly in patients where SCD is identified as the cause of ESKD.

Calciphylaxis-Associated Cutaneous Vascular Calcification in Noncalciphylaxis Patients.

Calciphylaxis is a highly morbid disease that is strongly associated with chronic kidney disease (CKD); however, the histologic criteria for diagnosis have not been well established nor have their specificity for calciphylaxis been determined. This retrospective study aimed to examine the prevalence of histologic features commonly associated with calciphylaxis in noncalciphylaxis patients. We also sought to evaluate whether these features may be more prevalent in patients with CKD. To assess this, healthy marginal skin tissue from above-the-knee amputation specimens was compared between patients with CKD (n = 23) and without CKD (n = 47). Intravascular calcification of capillaries or small-to-medium arterioles was detected on von Kossa stain in 40.0% of the entire cohort. Capillary calcification and intravascular thrombosis were more prevalent in patients with CKD. Finely stippled capillary calcification was present in 26.1% of patients with CKD versus 8.5% of patients without CKD (P = 0.0484), and intravascular thrombosis was present in 8.7% of patients with CKD and 0.0% of patients without CKD (P = 0.0403). None of the patients in this study had clinical evidence of calciphylaxis at presentation and in at least a 1-year follow-up period. This study confirms that the histologic features previously associated with calciphylaxis are nonspecific and are more prevalent in patients with CKD.

Revisiting therapeutic options for calciphylaxis.

PURPOSE OF REVIEW: Calciphylaxis is a disorder of cutaneous microvascular calcification and thrombosis leading to chronic, excruciatingly painful, progressive wounds with a high risk of sepsis and death. The diagnosis and treatment of calciphylaxis presents significant challenges. A poorly understood disease, the management of calciphylaxis has mostly been restricted to wound management and a few novel therapies. Data from patient registries and new studies on causal pathways is stimulating the development of pathogenesis-based medical therapies. RECENT FINDINGS: Much needed clinical trials are now underway to examine the safety and efficacy of sodium thiosulfate and other therapeutics for the indication of calciphylaxis. There is emerging data suggesting a potential role of therapeutic anticoagulation in these patients. There has also been a renewed emphasis on patient-oriented outcomes, such as improvement of pain scores and quality-of-life indices. SUMMARY: This review highlights ongoing clinical trials studying therapeutic options in calciphylaxis and emphasizes the causal pathways that led to the development of such therapies.

Factors associated with false-negative pathologic diagnosis of calciphylaxis.

BACKGROUND: Calciphylaxis is a rare, painful, and debilitating disorder of vascular calcification and skin necrosis that typically affects patients with advanced kidney disease. During our routine pathology practice, we noted several missed diagnoses on calciphylaxis consultation cases originating from outside institutions and sought to explore factors associated with false-negative pathologic diagnosis of calciphylaxis. METHODS: The pathology database of a large tertiary academic medical center was retrospectively searched for "calciphylaxis" in inside reports on outside surgical consultation cases between 2007 and 2017. Inside and outside pathology reports were compared and medical records were searched for calciphylaxis clinical diagnosis and risk factors. RESULTS: Twenty-four calciphylaxis patients were identified, with median age of 63.5 years. Seven of 24 (29%) of specimens were inadequate (e.g., lack of subcutaneous adipose tissue for evaluation). Eight of 17 (47%) of adequate specimens had a first false-negative pathologic diagnosis of calciphylaxis. Histochemical staining for calcium significantly correlated with true-positive diagnosis (93% vs 55%, P = 0.004). Dermatopathology fellowship training significantly correlated with true-positive diagnosis (82% vs 38%, P = 0.047). CONCLUSIONS: Adequate sampling, dermatopathology training, and use of histochemical stains to identify calcium associate with decreased false-negative rate for calciphylaxis diagnosis. These findings need further evaluation in larger prospective studies.

Sickle Cell Nephropathy in the Pediatric Population.

BACKGROUND: Compared to the past, patients with sickle cell disease (SCD) currently live longer due to improvements in diagnosis and comprehensive care. Due to these advances, long-term chronic complications pose a greater challenge in the management of patients with SCD. In particular, sickle cell nephropathy (SCN) is associated with significant morbidity and mortality across all age groups. Furthermore, SCN is an understudied condition with relatively few symptoms and therefore requires close surveillance. In this review, we sought to explore the epidemiology, natural history, and treatment options for SCN with an emphasis on the pediatric population. SUMMARY: SCN invariably begins in childhood with evidence of structural changes detected as early as infancy. These indolent changes can progress undetected to advanced chronic kidney disease by late adolescence or early adulthood. The risk factors for progression are not well defined, but significant albuminuria (which is also the most common presentation in childhood) is a key factor in progression. One of the main challenges in understanding SCN in children is the poor correlation between estimated and measured glomerular filtration rates. Another challenge is the lack of large-scale longitudinal studies that track the clinical outcomes of pediatric patients over time. Several studies aim to identify early biomarkers of SCN in children, as albuminuria presents only following significant chronic damage. The utility of angiotensin converting enzyme inhibitors and hydroxyurea in treating albuminuria is addressed here as well as novel treatments that may be of benefit.

Cutaneous calcification in patients with kidney disease is not always calciphylaxis.

Calciphylaxis, also referred to as calcific uremic arteriolopathy, is a rare disorder that predominantly afflicts patients with end-stage renal disease. In this issue of Kidney International, a report describing histologic features of calciphylaxis questions the specificity of histologic findings typically considered to be characteristic of calciphylaxis. Validated diagnostic criteria are much needed for the clinical care and the investigational studies of patients with calciphylaxis.