Concentrating defect, urinary

Yang, B., Ma, T., Dong, J. Y. and Verkman, A. S. (2000). Partial correction of the urinary concentrating defect in aquaporin-1 null mice by adenovirus-mediated gene delivery. Hum. Gene Ther. 11, 567-575. 

The other case history was an example of the complete opposite. Here, low urine concentrations were observed in spite of obvious excessive exposure and moderate cholinesterase decline. This was a 49-year-old agricultural sprayman whose techniques were atrocious and protection was minimal. In spite of these practices, however, urine concentrations were always below the 1-p.p.m. level of PNP. It was also noted that, although not drinking excessively, over an 80-day period he failed to concentrate his urine above isotonic levels, suggesting some underlying urinary concentration defect. Correction of his urine to osmotic levels observed in other spraymen would have raised his PNP level to 5 p.p.m. Subsequent evaluation confirmed the presence of proximal and distal renal tubular dysfunction. 

Aquaporin 2 Collecting duct Severe urinary concentrating defect [189]... 

Rojek A, Fuchtbauer EM, Kwon TH, Frokiaer J, Nielsen S Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice. Proceedings of the National Academy of Sciences of the United States of America 103 6037-6042,2006... 

In persons with normal kidney function, sodium balance is maintained at a sodium intake of 120 to 150 mEq/day. The fractional excretion of sodium (FENa) is approximately 1% to 3%. Water balance is also maintained, with a normal range of urinary osmolality of 50 to 1200 mOsm/L. In patients with severe CKD (Stages 4 and 5), sodium balance is achieved, but results in a volume-expanded state. FENa may increase to as much as 10% to 20%, possibly due to increased concentrations of atrial natriuretic peptide. An osmotic diuresis occurs with an increase in FENa leading to obligatory water losses and impairment in the kidney s ability to dilute or concentrate urine (urinary osmolality is often fixed at that of plasma or approximately 300 mOsm/L). Nocturia is present relatively early in the course of CKD (Stage 3) secondary to the defect in urinary concentrating ability. Total renal sodium excretion decreases despite an increase in sodium excretion by remaining nephrons. Volume overload with pulmonary edema can result, but the most common manifestation of increased intravascular volume is systemic hypertension. ... 

Patients with nephrogenic diabetes insipidus often have polydipsia and polyuria (see Chap. 49). They adapt well to their urinary-concentrating defect and these concerns are usually minimal. Acute tubular necrosis is frequent in the setting of acute hthium toxicity. Urinalysis may show moderate proteinuria, a few red and white blood cells, and granular casts. Renal function usuahy returns to baseline values after hthium concentrations are reduced to the therapeutic range. Nephrotoxicity may develop insidiously and be recognized by rising BUN or creatinine concentrations or the onset of hypertension. The urinalysis may show mild proteinuria and a few red and white blood cells. 

Urinary excretion of N-acetylaspartate is elevated and the cerebrospinal fluid concentration may be 50 times control values. The cause is a deficiency of aspartoacylase, which cleaves N-acetylaspartate to form aspartate and acetyl-CoA. The enzyme occurs primarily in the white matter, but N-acetylaspartate is most abundant in gray matter. The defect is expressed in skin fibroblasts. 

Approximately two thirds of kidney stones contain Ca2+ phosphate or Ca2+ oxalate. Many patients with such stones exhibit a defect in proximal tubular Ca2+ reabsorption that causes hypercalciuria. This can be treated with thiazide diuretics, which enhance Ca2+ reabsorption in the distal convoluted tubule and thus reduce the urinary Ca2+ concentration. Salt intake must be reduced in this setting, since excess dietary NaCI will overwhelm the hypocalciuric effect of thiazides. Calcium stones may also be caused by increased intestinal absorption of Ca2+, or they may be idiopathic. In these situations, thiazides are also effective, but should be used as adjunctive therapy with other measures. 

Male patients affected with X-linked Cr transporter defect have elevated urinary Cr concentrations only if this is expressed per mol creatinine (also mentioned Cr creatinine ratio). In plasma, Cr concentrations are within the normal limits. Also, GA is within the reference range in both plasma and urine. Female carriers of the defect may have elevated urinary Cr excretion (expressed per mol creatinine). However this is not a consistent finding in all carriers. 

The disturbance of copper excretion, primarily due to a defect in the billiary excretion, is consistent with the biochemical findings in patients with Wilson disease. Urinary copper excretion is increased owing to total body overload of copper. Renal dysfunction includes albuminuria and renal rickets. Incorporation of copper in ceruloplasmin is impaired. Thus, there is a greater proportion of copper bound to albumin and amino acid complexes in the serum. But the overall copper concentration in serum is low. Ceruloplasmin is a multicopper oxidase see Copper Proteins Oxidases) that... 

Clinical evidence suggestive of analgesic nephropathy includes nocturia, renal insufficiency with severe acidosis, persistent urinary tract infection with colic, hematuria, and hypertension (40,41). Nocturia resulting from failure to concentrate urine is usually the earliest functional defect, but like the other symptoms it is non-specific, rendering the diagnosis of analgesic nephropathy difficult. A CT scan showing bilateral small kidneys with bumpy contours, and papillary calcification is accepted to be of sufficient specificity (38,39). 

---