Idiopathic recurrent calcium urolithiasis (IRCU): variation of fasting urinary protein is a window to pathophysiology or simple consequence of renal stones in situ?

Abstract

BackgroundIn IRCU it is uncertain whether variation of urinary protein, especially non-albumin protein (NAlb-P), is due to the presence of stones or reflects alteration of oxidative metabolism.AimsTo validate in a tripartite cross-sectional study of 187 ambulatory male patients, undergoing a standardized laboratory programme, whether stones impact on N-Alb-P or the state of oxidative metabolism interferes with IRCU pathophysiology.MethodsIn part 1 the strata low and high of fasting urinary excretion rate per 2 h of N-Alb-P, malonedialdehyde, hypoxanthine, xanthine, pH and other urine components were compared, and association with renal stones in situ evaluated; in part 2 the co-variation of oxidatively modulated environment, fasting urinary pH, calcium (Ca) salt crystallization risk and the number of patients with stones in situ was examined; in part 3, the nucleation of Ca oxalate and Ca phosphate was tested in undiluted postprandial urine of patients and related to the state of oxidative metabolism.ResultsIn part 1, N-Alb-P excretion > 4.3 mg was associated with increase of blood pressure, excretion of total protein, hypoxanthine (a marker of tissue hypoxia), malonedialdehyde (a marker of lipid peroxidation), sodium, magnesium, citrate, uric acid, volume, pH, and increase of renal fractional excretion of both NAlb-P and uric acid; when stones were present, urinary pH was elevated but other parameters were unaffected. Significant predictors of N-Alb-P excretion were malonedialdehyde, fractional N-Alb-P and hypoxanthine. In part 2, urine pH > 6.14 was associated with unchanged blood pressure and plasma vasopressin, increase of blood pH, urinary volume, malonedialde hyde, fractional excretion of N-Alb-P, uric acid, Ca phosphate, but not Ca oxalate, supersaturation; this spectrum was accompanied by decrease of concentration of urinary total and free magnesium, total and complexed citrate, plasma uric acid (in humans the major circulating antioxidant) and insulin; the number of stone-bearing patients was increased. Significant predictors of urine pH were body mass index, plasma insulin and uric acid (negative), and urinary xanthine (positive). In part 3 low plasma uric acid, not high urinary malonedialdehyde or high ratio malonedialdehyde/uric acid was significantly associated with diminished Ca but not oxalate tolerance, with the first nucleating crystal type being mostly Ca phosphate (hydroxyapatite), in the rest Ca oxalate dihydrate; uricemia correlated marginally positively (p = 0.055) with Ca tolerance of urine, stronger with blood pressure and insulin, and negatively with urinary xanthine, fractional N-Alb-P, volume, sodium.ConclusionsIn IRCU 1) not renal stones in situ, but disturbed oxidative metabolism apparently modulates nephron functionality, ending up in higher renal NAlb-P release, urinary volume, sodium and pH of fasting urine; 2) etiologically unknown decline of uricemia may represent antioxidant deficiency and cause a risk of hydroxyapatite crystallization and stone formation in a weakly acidic or a...

Association of non-alcoholic fatty liver disease with renal stone disease detected on computed tomography

“…The association between NAFLD and renal stone disease has received little attention. In the review of recent literature, oxidative and systemic metabolisms are compatible with stone formation [16] . The kidneys is an highly vulnerable organ damaged by reactive oxygen species, likely due to the abundance of long chain poly unsaturated fatty acids in the composition of renal lipids and systemic oxidative species can result in peroxidation of lipid that may have an effect in calcium oxalate stone formation [16] .…”

“…In the review of recent literature, oxidative and systemic metabolisms are compatible with stone formation [16] . The kidneys is an highly vulnerable organ damaged by reactive oxygen species, likely due to the abundance of long chain poly unsaturated fatty acids in the composition of renal lipids and systemic oxidative species can result in peroxidation of lipid that may have an effect in calcium oxalate stone formation [16] . Further data suggest that fatty liver may result in changes in urinary constituents, leading to an increased incidence of stone formation [17] .…”

Idiopathic recurrent calcium urolithiasis (IRCU): pathophysiology evaluated in light of oxidative metabolism, without and with variation of several biomarkers in fasting urine and plasma - a comparison of stone-free and -bearing male patients, emphasizing mineral, acid-base, blood pressure and protein status*

“…The overlap of patients in present and previous work, following substantially different strategies [ 19 , 20 ], was about 95%. The study was retrospective, observational, cross-sectional and correlative (healthy control individuals were not included).…”

“…The following uncontrolled study is an extension of, and to some degree summarizing, our previous reports in this area [11,16-20]. The focus was on several questions: 1) are the levels of bio markers (see below) different, depending on whether SF or SB patients are studied; if not, in which other regards arc these subsets of patients different; 2) are traditional Ca stone risk parameters subject to modulation by variation of bio markers; 3) which factors influence the frequency distribution of SF and SB patients; 4) study of interrelationships of variables and, if helpful in understanding events involved in formation of new Ca stone, to comment a possible initiating role of OM.…”

NAFLD and Extra-Hepatic Comorbidities: Current Evidence on a Multi-Organ Metabolic Syndrome

“…Hyperuricemia is a frequent finding among NAFLD patients, and it is well-known that insulin resistance may decrease urinary ammonia synthesis and excretion, resulting in lower urinary pH and creating favorable conditions for the formation of uric acid stones [213,214]. Furthermore, idiopathic calcium urolithiasis seems to be induced by altered oxidative stress, increasing renal non-albumin protein excretion and reducing urinary ammonia, resulting in higher hydroxyapatite crystallization and stone formation [215]. As touched on previously, NAFLD and MetS are characterized by persistent, low-grade inflammation and the resulting oxidative stress may damage the kidney parenchyma through lipid peroxidation of long-chain poly-unsaturated fatty acids, increasing the risk of calcium oxalate stone formation [216].…”