Determinants of urinary excretion of Tamm–Horsfall protein in non‐selected kidney stone formers and healthy subjects

Abstract

The aim of the study was to measure urinary excretion of Tamm-Horsfall protein (THP), an important inhibitor of crystallization, and to identify possible determinants of urinary THP excretion in non-selected kidney stone formers (SF) and healthy subjects (C). By means of a commercially available ELISA (Pharmacia and Upjohn/Elias, Germany), we measured THP in 24-h urines of 104 SF (74 males/30 females, age 16-74 years) who had formed 8.7+/-2.4 stones (range 1-240), and of 71 C (41 males/30 females, age 22-62 years). Types of stones formed by SF were 88 calcium, eight uric acid, six infection, and two cystine. All values are means+/-SE. The normal range (5th to 95th percentile) of U(THP)xV was 9.3-35.0 mg/day in males and 9.0-36.3 mg/day in females respectively. Mean U(THP)xV was 21.3+/-1.2 mg/day (range 3. 4-51.6) in male and 15.2+/-1.6 mg/day (range 1.8-32.3) in female SF (P=0.008 vs male SF). Since U(THP)xV was positively correlated with C(Crea) (r=0.312, P=0.001) in SF as well as with U(Crea)xV (r=0.346, P=0.0001) and with body surface (r=0.271, P=0.0003) in all study subjects, mean THP/Crea (mg/mmol) was used for all further calculations. Overall, THP/Crea was lower in SF (1.42+/-0.07 vs 1. 68+/-0.08, P:=0.015), mainly due to increased THP/Crea in female C (2.08+/-0.11, P=0.0036 vs female SF, P=0.0001 vs male C and vs male calcium SF), which also explains decreased THP/Crea values in calcium SF (1.46+/-0.08, P=0.041 vs C). In addition, THP/Crea was reduced in uric acid SF (1.11+/-0.21, P=0.049 vs C). Whereas THP/Crea was not related to age, urine volume, intake of dairy calcium, or urinary markers of protein intake, either in C or in SF, it correlated significantly with urinary Citrate/Crea, both in C (r=0.523, P=0.0001) and in SF (r=0.221, P=0.025). In C only, but not in SF, THP/Crea was correlated with urinary Calcium/Crea (r=0. 572, P=0.0001) and with Oxalate/Crea (r=0.274, P=0.022). Both in C and SF, urinary THP excretion is related to body size, renal function and urinary citrate excretion, whereas dietary habits apparently do not affect THP excretion. Uric acid and calcium stone formation predict reduced THP excretion in comparison with C, whereas female gender goes along with increased urinary THP excretion in C. Possibly most relevant to kidney stone formation is the fact that THP excretion rises only in C in response to increasing urinary calcium and oxalate concentrations, whereas this self-protective mechanism appears to be missing in SF.