Familial hypocalciuric hypercalcemia as a differential diagnosis of primary hyperparathyroidism with negative images

Introduction. Familial hypocalciuric hypercalcemia is a rare inherited calcium metabolism disorder in which an alteration of the parathyroid hormone secretion set-point causes hypercalcemia with relative hypocalciuria. Some data suggest that its prevalence is around 74.1 per 100,000 inhabitants. Often, patients are asymptomatic. However, they can develop mild symptoms and an overactive parathyroid adenoma, its main differential diagnosis. The objective was to describe a patient’s case and highlight the importance of clinical suspicion and diagnosis to avoid unnecessary surgical neck explorations for parathyroid adenomas. Case report. This is the case of a 40-year-old man with a biochemical profile compatible with primary hyperparathyroidism with anatomical and functional images negative for adenoma and a calcium/creatinine clearance ratio below 0.001, considering familial hypocalciuric hypercalcemia. Genetic studies evidence a mutation in the calcium sensor receptor gene and confirm the diagnosis. Discussion. Familial hypocalciuric hypercalcemia’s main differential diagnosis is an overactive parathyroid adenoma. For both, mild or no symptoms may be present; serum calcium exceeds the upper limit, and parathormone is more than 25pg/ml. The calcium/creatinine clearance ratio should be used to differentiate one from the other and avoid unnecessary surgical neck explorations. Besides the lack of information on this topic, evidence supports the use of calcimimetics to treat symptomatic hypercalcemia. Conclusions. Patients with mild hypercalcemia with parathyroid hormone readings above 25pg/ml and a calcium/creatinine clearance ratio below 0.001, or patients with primary hyperparathyroidism with negative imaging, should not undergo surgical neck explorations. In these cases, familial hypocalciuric hypercalcemia is a reliable diagnosis; Cinacalcet may be administered in cases of symptomatic hypercalcemia.

Protective Actions of Cilnidipine: Dual L/N-Type Calcium Channel Blocker Against Hypertensive Renal Injury in Rats

Background: Cilnidipine belongs to fourth generation dihydropyridine calcium channel blocker (CCB). It is a dual L & N-type CCB. L- type calcium channels are present on the vascular smooth muscle and N-type calcium channels are present on the presynaptic nerve terminals. Cilnidipine has a vasodilating effect, its action is slow and long lasting. Aim and objectives: Aim of present study was to demonstrate the beneficial effects of cilnidipine on the hypertensive renal injury rats. And our objectives is to assess renal injury parameters (Proteinuria, Creatinine clearance, Renal fibrosis/glomerulosclerosis) in response to chronic NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) treatment in the presence or absence of cilnidipine treatment. Material and methods: Male albino Wister rats were procured from institutional animal house, divided into 4 groups (n=6 in each group). Group1 treated with vehicle (control), group2 treated with cilnidipine, group3 treated with L-NAME, group4 treated with L-NAME & cilnidipine. 24 hour urinary protein and creatinine clearance were measured. Serum urea and creatinine levels are also measured. Urinary and serum Angiotensin II levels were measured. Histopathological examination of kidneys was performed. Results: Our results demonstrate that treatment with cilnidipine (group4) there is reduction in 24hr urinary protein, improvement in creatinine clearance. We observed there was renal glomerulosclerosis and tubular degeneration of kidney tubules in group3 rats and reduction of renal injury in group4 rats. We also found reduced urinary and serum Angiotensin II level in cilnidipine treated (group 4) rats. Conclusion: These findings indicated that cilnidipine act as renoprotective agent and reduces glomerular damage in L-NAME induced hypertensive rats.

Prediction of Chemotoxicity, Unplanned Hospitalizations and Early Death in Older Patients with Colorectal Cancer Treated with Chemotherapy

Purpose: To identify risk factors for toxicity, unplanned hospitalization (UH) and early death (ED) in older patients with colorectal carcinoma (CRC) initiating chemotherapy. Methods: 215 patients over 70 years were prospectively included. Geriatric assessment was performed before treatment, and tumor and treatment variables were collected. The association between these factors and grade 3–5 toxicity, UH and ED (<6 months) was examined by using multivariable logistic regression. Score points were assigned to each risk factor. Results: During the first 6 months of treatment, 33% of patients developed grade 3–5 toxicity, 31% had UH and 23% died. Risk factors were, for toxicity, instrumental activities of daily living, creatinine clearance, weight loss and MAX2 index; for UH, Charlson Comorbidity Score, creatinine clearance, weight loss, serum albumin, and metastatic disease; and for ED, basic activities in daily living, weight loss, metastatic disease, and hemoglobin levels. Predictive scores were built with these variables. The areas under receiver operation characteristic (ROC) curves for toxicity, UH and ED were 0.70 (95% CI: 0.64–0.766), 0.726 (95% IC: 0.661–0.799) and 0.74 (95% IC: 0.678–0.809), respectively. Conclusion: Simple scores based on geriatric, tumor and laboratory characteristics predict severe toxicity, UH and ED, and may help in treatment planning.

Performance of creatinine-based equations for estimating glomerular filtration rate compared to endogenous creatinine clearance

Introduction: The guidelines recommend estimating the glomerular filtration rate using serum creatinine-based equations as a predictor of kidney disease, preferably adjusted for local population groups. Methods: Cross-sectional study that evaluated the performance of four equations used for estimating GFR compared to endogenous creatinine clearance (ClCr) in 1,281 participants. Modification of Diet equations in Renal Disease Study Group (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI with adjustment for local population (CKD-EPI local) and Full Age Spectrum (FAS) in comparison with endogenous creatinine clearance (ClCr). We used the Quantile Regression to calculate the median bias, interquartile range (IQR), Bland-Altman agreement analysis and 30% margin of error (P30). Results: The mean age of participants was 52.5 ± 16.5 years with 466 women (38%), median ClCr[IQR] of 92.0 [58.0; 122.0] mL/min/1.73 m2, with 320 (25%) participants presenting ClCr < 60 mL/min/1.73 m2. The performance of the local CKD-EPI and FAS equations were superior to MDRD and CKD-EPI in relation to variability (0.92 [0.89; 0.94]) and P30 (90.5% [88.7; 92, 0]). In the group with ClCr < 60 mL/min/1.73 m2, the local CKD-EPI and FAS equations showed less variability than the CKD-EPI and MDRD (0.90 [0.86; 0.98] and 1.05 [0.97; 1.09] vs. 0.63 [0.61; 0.68] and 0.65 [0.62; 0.70], P < 0.01) and best P30 (85.5) % [81.0; 90.0], 88.0% [84.0; 92.0] vs. 52.0% (46.0; 58.0) and 53.0% [47.0; 58 .5], P < 0.01). Conclusion: Local CKD-EPI and FAS equations performed better than CKD-EPI and MDRD when compared to ClCr.

374 Volume of contrast to creatinine clearance ratio predicts early mortality and AKI after TAVI

Aims The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established. Methods and results A large retrospective multicentre cohort of 1381 patients treated with TAVI was analysed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and one year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (HR: 1.16, 95% CI: 1.09–1.22, P &lt; 0.0001). Importantly, CV/CrCl was associated with the adverse outcome independently from the presence of baseline CKD (p for interaction = 0.22). CV/CrCl was independently associated with the individual components of the composite primary outcome including AKI (OR: 1.18, 95% CI: 1.08–1.28, P &lt; 0.0001) and 90 days mortality (HR: 1.90, 95% CI: 1.01–3.60, P = 0.047) after TAVI. AKI (HR: 1.94, 95% CI: 1.21–3.11, P = 0.006) but not CV/CrCl was associated with the risk of 1-year mortality after TAVI. Conclusions CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI.

554 Machine learning for prediction of in-hospital mortality in COVID-19 patients: results from an Italian multicentre study

Aims Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Prediction models are needed to optimize clinical management and to early stratify patients at a higher mortality risk. Machine learning (ML) algorithms represent a novel approach to identify a prediction model with a good discriminatory capacity to be easily used in clinical practice. Methods and results The Cardio-COVID is a multicentre observational study that involved a cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 [by real time reverse transcriptase—polymerase chain reaction (RT-PCR)] who were hospitalized in 13 Italian cardiology units from 1 March to 9 April 2020. Patients were followed-up after the COVID-19 diagnosis and all causes in-hospital mortality or discharge were ascertained until 23 April 2020. Variables with more than 20% of missing values were excluded. The Lasso procedure was used with a λ = 0.07 for reducing the covariates number. Mortality was estimated by means of a Random Forest (RF). The dataset was randomly divided in two subsamples with the same percentage of death/alive people of the entire sample: training set contained 80% of the data and test set the remaining 20%. The training set was used in the calibration procedure where a RF models in-hospital mortality with the covariates selected by Lasso. Its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity, and related 95% confidence interval (CI) computed with 10 000 stratified bootstrap replicates. From the RF the relative Variable Importance Measure (relVIM) was extracted to understand which of the selected variables had the greatest impact on outcome, providing a ranking from the most (relVIM = 100) to the less important variable. The model obtained was compared with the Gradient Boosting Machine (GBM) and with the logistic regression, where the predictions were cross validated. Finally, to understand if each model has the same performance in sample (training) and out of sample (test), the two AUCs were compared by means of the DeLong’s test. Among 701 patients enrolled (mean age 67.2 ± 13.2 years, 69.5% males), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9–24) days. Variables selected by the Lasso were: age, Oxygen saturation, PaO2/FiO2, Creatinine Clearance and elevated Troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, a lower creatinine clearance levels and higher prevalence of elevated Troponin (all P &lt; 0.001). Training set included 561 patients and test set 140 patients. The best performance out of sample was provided by the RF with an AUC of 0.78 (95% CI: 0.68–0.88) and a sensitivity of 0.88 (95% CI: 0.58–1.00). Moreover, RF is the unique methodology that provided similar performance in sample and out of sample (DeLong test P = 0.78). On the contrary, prediction model was less accurate by using GBM and logistic regression. The relVIM ranked the variables from the most to the less important in predicting the outcome as follows: clearance creatinine, PaO2/FiO2, age, oxygen saturation, and elevated Troponin. Conclusions In a large COVID-19 population, we showed that a customizable ML-based score derived from clinical variables, is feasible and effective for the prediction of in-hospital mortality.

Evaluation and enhancement of standard equations for renal function estimation in individuals with components of metabolic disease

Background The primary objective of this study aims to test patient factors, with a focus on cardiometabolic disease, influencing the performance of the Cockcroft-Gault equation in estimating glomerular filtration rate. Methods A cohort study was performed using data from adult patients with both a 24-h urine creatinine collection and a serum creatinine available. Creatinine clearance was calculated for each patient using the Cockcroft-Gault, Modified Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations and estimates were compared to the measured 24-h urine creatinine clearance. In addition, new prediction equations were developed. Results In the overall study population (n = 484), 44.2% of patients were obese, 44.0% had diabetes, and 30.8% had dyslipidemia. A multivariable model which incorporating patient characteristics performed the best in terms of correlation to measured 24-h urine creatinine clearance, accuracy, and error. The modified Cockcroft-Gault equation using lean body weight performed best in the overall population, the obese subgroup, and the dyslipidemia subgroup in terms of strength of correlation, mean bias, and accuracy. Conclusions Regardless of strategy used to calculate creatinine clearance, residual error was present suggesting novel methods for estimating glomerular filtration rate are urgently needed.

Obesity Related Glomerulopathy in adolescent women: the effect of Body Surface Area

Background: Adolescent obesity, a risk factor for cardio-renal morbidity in adulthood, has reached epidemic proportions. Obesity-related glomerulopathy (ORG) has an early reversible stage of hyperfiltration. Age-appropriate formulae for estimated glomerular filtration rate (eGFR), which are standardized to ideal body surface area (BSA) and provide assessment of kidney function in mL/min/1.73 m2 units, may underestimate prevalence of early ORG. We investigated whether adjusting eGFR to actual BSA more readily identifies early ORG. Methods: We studied a cohort of 22,417 young individuals ages 12-21 years from a New York metropolitan multi-institutional electronic health records clinical data base. eGFR was calculated in two ways: BSA-standardized eGFR; and absolute eGFR. Hyperfiltration was defined above a threshold of 135mL/min/1.73 m2 or 135 mL/min, respectively. The prevalence of hyperfiltration according to each formula was assessed in parallel to creatinine clearance. Results: Serum creatinine values and hyperfiltration prevalence according to BSA-standardized eGFR were similar, 13.4-15.3%, across Body Mass Index (BMI) groups. The prevalence of hyperfiltration determined by absolute eGFR differed across BMI groups: Underweight - 2.3%; Normal 6.1%; Overweight - 17.4%; Obese - 31.4%. This trend paralleled the rise in creatinine clearance across BMI groups. Conclusions: Absolute eGFR more readily identifies early ORG than the currently used formulae, which are adjusted to a standardized BSA, not representative of current population BMI measures. Using Absolute eGFR in clinical practice and research may improve the ability to identify, intervene and reverse early ORG, which has great importance with increasing obesity rates.