Beneficial Extracardiac Effects of Cardiovascular Medications

: Cardiovascular diseases are the most common cause of death worldwide, with cardiovascular medications being amongst the most common medications prescribed. These medications have diverse effects on the heart, vascular system as well as other tissues and organ systems. The extra cardiovascular effects have been found to be of use in the treatment of non-cardiovascular diseases and pathologies. Minoxidil is used to manage systemic hypertension with its well-known side effect of hirsutism used to treat alopecia and baldness. Sildenafil was originally investigated as a treatment option for systemic hypertension however its side effect of penile erection led to it be widely used for erectile dysfunction. Alpha-1 blockers such as terazosin are indicated to treat systemic hypertension but are more commonly used for benign prostatic hyperplasia and post-traumatic stress disorder. Beta blockers are the mainstay treatment for congestive heart failure and systemic hypertension but have found use to help in patients with intention tremors as well as prophylaxis of migraines. Similarly, calcium channel blockers are indicated in medical expulsion therapy for ureteric calculi in addition to their cardiovascular indications. Thiazides are commonly used for treating systemic hypertension and as diuretics. Thiazides can cause hypocalciuria and hypercalcemia. This side effect has led to thiazides being used to treat idiopathic hypercalciuria and associated nephrolithiasis. Spironolactone is commonly utilized in treating heart failure and as a diuretic for edema. It’s well described anti-androgen side effects have been used for acne vulgaris and hirsutism in polycystic ovarian syndrome. This review article discusses how the various extra-cardiovascular effects of commonly used cardiovascular medications are put to use in managing non-cardiovascular conditions.

Prevalence and Pathophysiology of Pediatric Urolithiasis - A Review

Urolithiasis is a condition in which hard deposits made of salts and minerals are accumulated inside the kidneys. A lot of studies demonstrated adult urolithiasis but studies on pediatric urolithiasis is still scarce. Studies had shown that pediatric urolithiasis prevalence is progressively increasing worldwide. The main cause for this increase is not totally clear but has been associated to changes in climate, nutritional habits and other environmental factors. Pediatric urolithiasis is distinctive and different from adult urolithiasis concerning prevalence, etiology and clinical presentation. Over the time while the condition was evolving, the main cause has changed from predominantly infectious to metabolic in nature. Pediatric urolithiasis should not be underestimated as it is associated with morbidity mainly since it possesses a striking feature which is ability to recur. Metabolic risk factors are more communal in pediatric urolithiasis than in adults. The common type of calculi in children is comprised of either calcium oxalate or calcium phosphate mainly and is often associated with a metabolic abnormality. Informed as metabolic abnormalities, Idiopathic hypercalciuria and hypocitraturia are the most frequently reported. A good understanding of the causes and risk factors of pediatric urolithiasis will provide better strategies and techniques for calculi treatment and prevention in children.

Metabolic Risk Factors in Patients with Kidney Stones with and without Type 2 Diabetes

Background: In the past few decades, the prevalence of kidney stones in Western countries has increased in parallel with the growing overweight/obesity and type 2 diabetes mellitus rates. An increased insulin resistance in these patients explains, in part, the rising prevalence of uric acid stones. The objective of this retrospective study is to evaluate the metabolic abnormalities in type 2 diabetic and non-diabetic patients with kidney stones. All patients were evaluated following an ambulatory protocol for kidney stones. Methods: A total of 104 diabetic patients (age: 57.8 ± 11 years) and 130 non-diabetic (age: 52.1 ± 6.7 years) patients with kidney stones were selected. Higher rates of body mass index, hypertension, urinary tract infection, gout and hyperuricemia were observed in diabetic patients as compared to the non-diabetics, while similar rates were found for their family history of kidney stones. Results: Urinary pH was lower in diabetic patients than in non-diabetic patients. Metabolic abnormalities were detected in 95.2% and 81.5% of diabetic and non-diabetic, respectively. Unduly acidic urine pH was the most frequent abnormality in diabetic patients while hyperuricosuria was the second more common abnormality. On the other hand, in non-diabetics patients idiopathic hypercalciuria was the most common metabolic abnormality followed by hyperuricosuria. Conclusions: The main risk factor for lithogenesis in type 2 diabetes is unduly acidic urine pH, followed by hyperuricosuria and idiopathic hypercalciuria.

The Activation of ROS/NF-κB/MMP-9 Pathway Promotes Calcium-Induced Kidney Crystal Deposition

Idiopathic hypercalciuria is an important risk factor for the formation of calcium-containing kidney stones. Matrix metalloproteinase-9 (MMP-9) is closely related to cell and tissue remodeling and is involved in ectopic tissue calcification. However, little is known about its role in kidney stone formation. In this study, we found that the expression of MMP-9 and that of osteoblastic-related proteins was increased in normal rat kidney epithelial-like (NRK-52E) cells following treatment with a high concentration of calcium, while the knockout or overexpression of MMP-9 could, respectively, significantly inhibit or upregulate the expression of osteoblastic-related proteins and calcium crystal deposition. In addition, apoptosis and calcium crystal deposition were significantly reduced in Sprague–Dawley rats with 1,25(OH)2D3-induced hypercalciuria following MMP-9 inhibitor I treatment. Furthermore, inhibiting reactive oxygen species (ROS) production or the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway significantly reduced calcium-induced MMP-9 expression and calcium crystal deposition. In summary, our results suggested that a high calcium concentration promotes epithelial–osteoblastic transformation and calcium crystal deposition in renal tubule cells by regulating the ROS/NF-κB/MMP-9 axis and identified a novel role for MMP-9 in regulating calcium-induced calcium crystal deposition in renal tubules.

The main ways of correcting idiopathic hypercalciuria in children

Introduction. Idiopathic hypercalciuria (IH) is one of the most common metabolic disorders in children and is one of the leading causes of calcium urolithiasis and osteoporosis. The strategic goal of treatment for IH is to reduce urinary calcium excretion. Materials and methods. The study included 93 IH children aged from 3 to 14 years with identified IH. At the first stage, IH children have been prescribed low sodium and high potassium diet with increased fluid intake for three months without additional drug therapy. For children with persistent IH at the second stage, the diet was supplemented daily with 1000-1500 mg of fish oil for children for 3 months. At the third stage of treatment, persistent IH patients were prescribed hydrochlorothiazide at a dose of 1 mg/kg for 3 months. After each stage of treatment, we analyzed IH’s manifestations in dynamics and monitored urinary calcium excretion by calcium/creatinine ratio (CCR). Results. Evaluation of clinical and laboratory manifestations of IH after the first stage of treatment showed the effectiveness of the diet in 59.1% of patients. Among 38 patients included in the second stage of therapy, the normalization of urinary calcium excretion was noted in 52.6% of cases. The third stage of therapy was performed in 18 patients (19% of the initial group of IH children patients). The normalization of CCR was achieved in 16 (88.9%) children. Conclusion. For the correction of IH in children, a step-by-step approach should be recommended, starting with recommendations on the drinking regimen and nutrition, then prescribing fish oil preparations and resorting to thiazide diuretics in the lack of an effect from the first stages of treatment.

Impact of Thyroid Disease on Bone Mineral Density Preservation in Patients With Osteoporosis and Idiopathic Hypercalciuria

Background: Idiopathic hypercalciuria (IHC) is associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fractures. It is not known if thyroid disease impacts the degree of urine and bone mineral abnormalities in patients with IHC and osteoporosis (OPO). Methods: Retrospective chart review from a private endocrinology clinic identified 62 consecutive patients with OPO (fragility fracture and/or t-score ≤-2.5 on bone density scan) and concomitant diagnosis of IHC (urine calcium > 4.0 mg/kg weight/d when intaking low-moderate calcium amounts). Patients were classified into two groups: those with thyroid disease (Thy+, if presence of autoimmune thyroid disease [AITD] with high antibody titers and/or long-term thyroid medication use) and those without (Thy-). Comparisons were made between the two groups for severity of renal disease (urine calcium) and bone disease (number of fragility fractures, and BMD response to therapy). Results: Of 55 women and 7 men identified with both OPO and IHC, 30 were Thy+ (4 with Graves’, 11 with confirmed Hashimoto’s, 13 taking levothyroxine for presumed Hashimoto’s and 2 with thyroid cancer), and 32 were Thy- (including 2 with type 1 DM, 1 with vitiligo, and 6 with non-toxic nodular goiters requiring biopsies). Thy+ were compared to Thy- with respect to: mean age (70.7 ± 7.3 vs. 70.8 ± 9.3 y), sex (97% vs. 81% women), 24-hr urine calcium at diagnosis (317 ± 75 vs. 311 ± 68 mg), presence of fragility fracture (50% vs. 59%), use of thiazide (83% vs. 78%), and use of anti-fracture pharmacotherapy (73% vs. 84%). 50 patients had adequate comparative longitudinal BMD data. A (+) BMD response was based on consistent increases in BMD and/or t-scores across all spine and hip sites, and a (-) BMD response was classified by decreased BMD and/or t-scores across all sites. For Thy+ vs. Thy- patients, there were 25% vs. 69% (+) BMD response, 38% vs. 12% (-) BMD response, 21% vs. 4% with no significant BMD response, and 17% vs. 15% with mixed BMD responses. Conclusions: In this group at high risk for future fragility fractures, much lower rates of BMD preservation was seen in the Thy+ as compared to the Thy- patients. Overall, AITD and medical thyroid disease was very common (48%) in this cohort of patients with IHC and OP. However, this high rate may be confounded by the selective nature of the specialty clinic population. Further research needs to delineate the impact of AITD and thyroid medication use on the progression and treatment of patients with IHC and OPO.