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Idiopathic recurrent calcium urolithiasis (IRCU): variation of fasting urinary protein is a window to pathophysiology or simple consequence of renal stones in situ? A tripartite study in male patients providing insight into oxidative metabolism as possible driving force towards alteration of urine composition, calcium salt crystallization and stone formation.
Eur J Med Res. 2009 Sep 01; 14(9):378-92.EJ

Abstract

BACKGROUND

In IRCU it is uncertain whether variation of urinary protein, especially non-albumin protein (N-Alb-P), is due to the presence of stones or reflects alteration of oxidative metabolism.

AIMS

To 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.

METHODS

In 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.

RESULTS

In 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 N-Alb-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, malonedialdehyde, 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.

CONCLUSIONS

In IRCU 1) not renal stones in situ, but disturbed oxidative metabolism apparently modulates nephron functionality, ending up in higher renal N-Alb-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 alkaline inhibitor-deficient and N-Alb-P-rich milieu; 3) several observations, linking oxidative and systemic metabolism, are compatible with Ca stone initiation beyond tubules.

Authors+Show Affiliations

Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen-Nürnberg, Germany. ml.rasenack@web.de.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19748857

Citation

Schwille, Paul O., et al. "Idiopathic Recurrent Calcium Urolithiasis (IRCU): Variation of Fasting Urinary Protein Is a Window to Pathophysiology or Simple Consequence of Renal Stones in Situ? a Tripartite Study in Male Patients Providing Insight Into Oxidative Metabolism as Possible Driving Force Towards Alteration of Urine Composition, Calcium Salt Crystallization and Stone Formation." European Journal of Medical Research, vol. 14, no. 9, 2009, pp. 378-92.
Schwille PO, Schmiedl A, Wipplinger J. Idiopathic recurrent calcium urolithiasis (IRCU): variation of fasting urinary protein is a window to pathophysiology or simple consequence of renal stones in situ? A tripartite study in male patients providing insight into oxidative metabolism as possible driving force towards alteration of urine composition, calcium salt crystallization and stone formation. Eur J Med Res. 2009;14(9):378-92.
Schwille, P. O., Schmiedl, A., & Wipplinger, J. (2009). Idiopathic recurrent calcium urolithiasis (IRCU): variation of fasting urinary protein is a window to pathophysiology or simple consequence of renal stones in situ? A tripartite study in male patients providing insight into oxidative metabolism as possible driving force towards alteration of urine composition, calcium salt crystallization and stone formation. European Journal of Medical Research, 14(9), 378-92.
Schwille PO, Schmiedl A, Wipplinger J. Idiopathic Recurrent Calcium Urolithiasis (IRCU): Variation of Fasting Urinary Protein Is a Window to Pathophysiology or Simple Consequence of Renal Stones in Situ? a Tripartite Study in Male Patients Providing Insight Into Oxidative Metabolism as Possible Driving Force Towards Alteration of Urine Composition, Calcium Salt Crystallization and Stone Formation. Eur J Med Res. 2009 Sep 1;14(9):378-92. PubMed PMID: 19748857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Idiopathic recurrent calcium urolithiasis (IRCU): variation of fasting urinary protein is a window to pathophysiology or simple consequence of renal stones in situ? A tripartite study in male patients providing insight into oxidative metabolism as possible driving force towards alteration of urine composition, calcium salt crystallization and stone formation. AU - Schwille,Paul O, AU - Schmiedl,A, AU - Wipplinger,J, PY - 2009/9/15/entrez PY - 2009/9/15/pubmed PY - 2009/11/5/medline SP - 378 EP - 92 JF - European journal of medical research JO - Eur. J. Med. Res. VL - 14 IS - 9 N2 - BACKGROUND: In IRCU it is uncertain whether variation of urinary protein, especially non-albumin protein (N-Alb-P), is due to the presence of stones or reflects alteration of oxidative metabolism. AIMS: To 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. METHODS: In 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. RESULTS: In 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 N-Alb-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, malonedialdehyde, 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. CONCLUSIONS: In IRCU 1) not renal stones in situ, but disturbed oxidative metabolism apparently modulates nephron functionality, ending up in higher renal N-Alb-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 alkaline inhibitor-deficient and N-Alb-P-rich milieu; 3) several observations, linking oxidative and systemic metabolism, are compatible with Ca stone initiation beyond tubules. SN - 0949-2321 UR - https://www.unboundmedicine.com/medline/citation/19748857/Idiopathic_recurrent_calcium_urolithiasis__IRCU_:_variation_of_fasting_urinary_protein_is_a_window_to_pathophysiology_or_simple_consequence_of_renal_stones_in_situ_A_tripartite_study_in_male_patients_providing_insight_into_oxidative_metabolism_as_possible_driving_force_towards_alteration_of_urine_composition_calcium_salt_crystallization_and_stone_formation_ L2 - https://eurjmedres.biomedcentral.com/articles/10.1186/2047-783x-14-9-378 DB - PRIME DP - Unbound Medicine ER -