Kidney International, Vol. 38 (1990), pp. 736—743
Chronic tubulo-interstitial nephritis: Correlation between structural and functional findings GARABED EKNOYAN, MARY ANNE MCDONALD, DEBRA APPEL, and LUAN D. TRUONG Renal Section, Department of Medicine, and Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
Much of the focus of the clinical and experimental study of any coexistent glomerular dysfunction. Over the past decade, renal disease has centered on disorders that primarily affect the the more descriptive and encompassing terms of tubulo-interglomeruli and vasculature of the kidney. It has, however, long stitial disease and tubulo-interstitial nephritis (TIN) have come been appreciated that certain forms of acute or chronic renal to be the preferred names used to identify this entity in which failure result from disorders that primarily affect the renal the dominant morphologic changes are restricted to the interinterstitium and tubules while sparing the glomeruli and vascu- stitium and tubules of the kidney, and whose hallmark of lature. The acute form of this type of lesion was first recognized disordered pathophysiology is abnormalities of tubular function in 1860 as a complication of B-hemolytic streptococcal infection [5]. in the report of a fatal case of scarlet fever, which at postThe list of diseases to which chronic TIN has been attributed
mortem examination revealed interstitial infiltration of the has been compiled empirically, on the basis of the expected kidney by lymphocytic cells in the absence of any evidence of clinicopathological features which are associated with this a suppurative bacterial infection of the renal parenchyma [1]. In syndrome. The frequency with which each of the implicated 1898 Councilman published his classic paper in which he diseases accounts for TIN is not established. In one study that described the acute renal lesions in a variety of systemic examined this issue in cases of chronic renal failure, TIN infections and termed them 'acute interstitial nephritis' [2]. The chronic form of this entity had traditionally been attributed to pyelonephritis, whether or not actual evidence of renal infection could be documented. It attracted little attention until the report of Spuhler and Zollinger on chronic interstitial nephritis in which they described the chronic lesion in cases other than pyelonephritis and pointed out that it was not an uncommon cause of chronic renal failure [3]. Subsequent work in this area clarified the differentiation of chronic interstitial nephritis from chronic pyelonephritis and led to the identification of analgesic abuse as a principal cause of the lesion [4].
accounted for the renal failure in 32% of the cases [6]. In the 101 patients with TIN who were reviewed, it was found that 11 were of undeterminate or idiopathic etiology, 31 had anatomic abnormalities causing obstruction of the urinary tract, 20 were due to analgesic abuse, 11 to nephrosclerosis, 9 to nephrolithiasis, one
degrees of tubular atrophy and degeneration. Glomerular
ments of tubular function and the clinical presentation are
each to sickle cell disease and tuberculosis, and 7 to multiple causes. In another study that examined this issue in a series of 363 cases of chronic renal failure, TIN accounted for 40.8% of the cases reviewed and emerged as the most common cause of renal failure. In this series, analgesic abuse nephropathy was the leading cause of TIN (32.5%), followed by obstruction Since then a motley group of diseases have come to be (19.6%), nephrosclerosis (13.5%), nephrolithiasis (8.1%), infecimplicated as a cause of chronic tubulo-interstitial nephritis. tion (1.4%), and a variety of other less common causes of TIN They have in common the altered morphologic features of the (7.4%) [7]. In both of these studies, the diagnosis of TIN was kidney and the natural course of the renal disease that develops. based on the clinical characteristics which were considered The principal morphologic features of the renal lesions are typical of TIN. One limitation imposed by this approach is that interstitial fibrosis, mononuclear cellular infiltration and varying TIN is actually a clinicopathological entity, in which derangechanges of sclerosis, atrophy and periglomerular fibrosis, while helpful in suggesting the presence of TIN, but a definite diagnosis absent initially, ultimately develop and are common features of can only be established by morphologic examination of the the end-stage kidney disease that occurs. The renal insuffi- renal tissue. Furthermore, whereas studies of the renal biopsy
ciency is slow to develop and the early manifestations of the renal involvement of these patients are those of tubular dysfunction. With progressive injury, reduction in glomerular filtration rate does occur. However, early in the course of the disease the characteristic features of glomerular dysfunction— edema, significant proteinuria, and hypertension—are absent and tubular dysfunction is almost always out of proportion to
© 1990 by the International Society of Nephrology
material have shown a close correlation of tubulo-interstitial lesions with abnormalities of renal function in an assortment of renal diseases [8, 9], there is a paucity of studies in which the morphologic findings are related to renal function in biopsy documented cases of chronic TIN. The present study was undertaken to examine chronic TIN
from a different perspective, that is, the diagnosis of TIN established by morphologic examination of renal tissue. The kidney biopsy of the cases reviewed had been performed to determine the cause of renal failure in patients presenting with
736
737
Eknoyan et a!: Chronic tubulo-interstitial nephritis
renal dysfunction on whom a definite diagnosis could not be established on clinical grounds. The study was designed to
Table 1. Morphologic features selected for semiquantitation of renal biopsy specimens
determine the clinical features present in these cases at the time
when the kidney biopsy was performed, and to examine the relation of the structural changes noted on biopsy with the degree of renal dysfunction present at the time that the renal tissue was obtained. Methods
The renal biopsy file of the Department of Pathology of Baylor College of Medicine Affiliated Hospitals was reviewed for cases coded as chronic TIN during the period covering 1971 through 1986. Eighty-four such cases were found among the 1,426 biopsies interpreted during this interval. Only 48 of these
were included in this study. The other 34 were excluded because the clinical records were incomplete or unobtainable in
9, preliminary review of the biopsies failed to confirm the diagnosis of definite TIN in 7, or the lesions noted on biopsy were those of arteriosclerosis in 20. The pathologic diagnosis of
TIN was accepted when there was predominantly chronic interstitial inflammation and interstitial fibrosis with dispropor-
tionally good preservation of glomeruli, and there was no primary glomerular or vascular disease. However, included in
the study group were four cases with primary glomerular diseases, in which the tubulo-interstitial damage was obviously severe and considerably more prominent than the glomerular lesions, rather than being obviously secondary to the glomerular lesions alone. Thus, severe TIN was present in association
Semiquantitation scales
Features Glomerular
Number of glomeruli in the biopsy Number of globally sclerotic glomeruli
Number of segmentally sclerotic glomeruli Periglomerular fibrosis
0 — 3°
Tubular
Tubular atrophy Acute tubulitis Chronic tubulitis Hyalin casts Cellular casts Interstitial Interstitial fibrosis Interstitial edema Interstitial inflammation Interstitial hemorrhage General patterns of involvement Vascular
0— 0— 0— 0— 0 — 3° 0— 0— 0— 0— d—
4b 1°
3°
p"
0 — 1° 0 — 3° 0—
Vasculitis Arteriolar thickening Arterial thickening
Abbreviations are: a 0 = absent, 1 = mild, 2 = moderate, 3 = severe; = no changes, 1 = less than 20%, 2 = 20—40%, 3 = 40—60%, 4 =
t) 0
more than 60% of biopsy surface shows the evaluated features; 0 = d absent, I = present; d = diffuse = more than 75% of biopsy surface shows changes; p = patchy = less than 75% of biopsy surface shows
with mesangial proliferative lupus nephritis (1 case), with changes. diabetic glomerulosclerosis (2 cases), and with focal segntental sclerosis in a patient with sickle cell disease. Morphological evaluation For light microscopy (LM), a portion of the biopsy was fixed
in 4% neutral buffered formalin or B5 fixative, embedded in paraffin, sectioned at 4 .tm, routinely stained with hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, and in selected cases with silver-methenamine technique. For immunofluorescent (IF) study, a portion of the biopsy was snap-
frozen, sectioned at 4 m, and stained with fluorescinated
stained with PAS was evaluated for surface area occupied by glomeruli, interstitial, vascular and tubular compartments. There was a good correlation between the morphometric and semiquantitative technique. Consequently, only the semiquantitative scores were used for correlation between morphologic, functional and clinical findings. Clinical evaluation
antibodies to IgG, 1gM, IgA, C3, C4 and fibrinogen. For electron Only cases on which adequate clinical data was available at microscopic (EM) study, the biopsy tissue blocks were fixed in the time of kidney biopsy were included in the study. The
3% glutaraldehyde at 4°, and post-fixed in osmium tetroxide. Survey sections cut at I m were stained with toluidine blue. Thin sections cut at 1 ILm were stained with lead citrate and uranyl acetate, and studied with a JOEL electron microscope (JEOL, Tokyo, Japan). LM study was done in all cases, IF in 37 cases, and EM in 38 cases. IF and EM studies, in general, did
records of these cases were reviewed, specifically for data pertinent to renal function. For purposes of this study the
diagnosis of analgesic abuse was made in patients who gave a definite history of excessive (over 1 g/day) analgesic intake prior to the onset of renal insufficiency; urate nephropathy in patients with a history of clinical gout or hyperuricemia (>9 not add significantly to the LM study, but were reviewed mg/dl) prior to the onset of renal failure; obstructive uropathy in primarily for the purpose of excluding the presence of primary patients with clinical or radiological evidence of congenital or acquired obstruction; infection was considered to be present if glomerular disease. In addition to the general LM examination, several specific the patient had repeatedly positive urine cultures in the absence features were selected for semiquantitative analysis according of other abnormalities; multiple myeloma in the presence of to the criteria outlined in Table 1. The number of sclerotic definite tissue and laboratory diagnosis of myeloma and no glomeruli was expressed as a percent of the number of glomer- other apparent cause of renal disease; sickle cell nephropathy uli available for evaluation which ranged from 6 to over 50. To on the basis of clinical and laboratory evidence of sickle validate the semiquantitative analysis, a pilot study was done hemoglobinopathy; and heavy metal toxicity from a history of on eight randomly chosen biopsies. For this purpose, the point long-term environmental exposure. Cases in which none of the counting technique utilizing a 1 x 1 cm occular reticule with 100 potential causes of TIN could be established were classified as points was utilized. The entire surface of the biopsy specimens idiopathic.
Eknoyan et al: Chronic tubulo-interstitial nephritis
738
Table 2. Clinical characteristics and diagnoses of patients with chronic tubulo-interstitial nephritis Primary diagnosis
Idiopathic Obstruction Hyperuricemia Infiltrative Analgesic abuse Arteriosclerosis Metabolic Immunologic Pyelonephritis Diabetes Totals
Serum creatinine
Sex
No. of patients
Male
8 4 6 2 4 2
12 10
6 6 4 4 2 2
Female 4 6 0 4 0 2
1
1
2
1 1
0 0 0
48
27
21
Age years
mg/dl
44.8
3.5 5.9
5.4 3.9 5.5 3.8 8.5
50.7
11.1
6.1
2.5 2.8
3 1.6
5.3
2.1
5.1
43.7 46.5
3.5 4.7
39.5 52.7
5.3
26 36 71 35
1 1
44.9
Secondary diagnosis
HTN
1.8
0.8
8 3
UTI
DM
2 5
2
UA —
1
1
1.9 1.5
6
—
1
2
2 3
1
1.0
—
0.6 2.3 12.4
1 I 1
— — — — —
0.7
26
10
1.3
OBST
— —
— — — — — —
— — — — — — — —
I — — — — —
4
1
I
I
=
— —
Abbreviations are: HTN, hypertension defined as blood pressure > 140/90 mm Hg; UTI, urinary tract infection; DM, hyperglycemia; UA, hyperuricemia of> 9 mg/dl; OBST, obstruction of urinary tract.
Statistical analysis
Table 3. Laboratory findings at the time of renal biopsy in 48 patients with chronic tubulo-interstitial nephropathy
Quantitative data, expressed as means SE, were compared
Data available
by analysis of variance (ANOVA) and by the Wilcoxon sequen-
tial rank test. Values were obtained in two-tailed fashion and considered significant if 50m1/min
them (4%) were over 70 years old. The average age of the patients was 44.9 2.1 years, for women it was 44.4 2.7
3/HPF) Pyuria (WBC's > 5IHPF) Positive urine cultures >iO organisms/mi Glycosuria Acidification defect
Percent
48 22 15
23% 26% 31%
17 19
43%
8
18%
24
11
>15 mI/mm 3.0 g/24 hr of the patients ranged from 20 to 71 years, about two-thirds of the patients (62.5%) were less than 50 years old and only two of Hematuria (RBC's >
No. of cases
44 38%
30 44
29
80% 20% 66%
44
21
48%
6
3.2 years. The lack of patients 43 28% 12 who were younger than 20 years is a reflection on the referral 44 11 25% pattern within our institution. Children and adolescents are 37 referred to a pediatric hospital, the biopsy material from which 12 32% T0 5.5 was not included in this study. The majority of the patients were Aciiification test 2 2 100% 40 27 68% white (83.3%), consisting of 66.6% caucasians, 16.6% hispan- Specific gravity < 1.015 ics, and 16.6% blacks. In 12 cases no potential cause of TIN could be established. In the remainder of cases 10 had obstruction, 6 hyperuricemia, 6 an infiltrative process, 4 analgesic abuse, 4 arteriosclerosis, 2 a metabolic abnormality, 2 an than 5.5, in the presence of acidemia (CO2
Chronic tubulo-interstitial nephritis: Correlation between structural and functional findings GARABED EKNOYAN, MARY ANNE MCDONALD, DEBRA APPEL, and LUAN D. TRUONG Renal Section, Department of Medicine, and Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
Much of the focus of the clinical and experimental study of any coexistent glomerular dysfunction. Over the past decade, renal disease has centered on disorders that primarily affect the the more descriptive and encompassing terms of tubulo-interglomeruli and vasculature of the kidney. It has, however, long stitial disease and tubulo-interstitial nephritis (TIN) have come been appreciated that certain forms of acute or chronic renal to be the preferred names used to identify this entity in which failure result from disorders that primarily affect the renal the dominant morphologic changes are restricted to the interinterstitium and tubules while sparing the glomeruli and vascu- stitium and tubules of the kidney, and whose hallmark of lature. The acute form of this type of lesion was first recognized disordered pathophysiology is abnormalities of tubular function in 1860 as a complication of B-hemolytic streptococcal infection [5]. in the report of a fatal case of scarlet fever, which at postThe list of diseases to which chronic TIN has been attributed
mortem examination revealed interstitial infiltration of the has been compiled empirically, on the basis of the expected kidney by lymphocytic cells in the absence of any evidence of clinicopathological features which are associated with this a suppurative bacterial infection of the renal parenchyma [1]. In syndrome. The frequency with which each of the implicated 1898 Councilman published his classic paper in which he diseases accounts for TIN is not established. In one study that described the acute renal lesions in a variety of systemic examined this issue in cases of chronic renal failure, TIN infections and termed them 'acute interstitial nephritis' [2]. The chronic form of this entity had traditionally been attributed to pyelonephritis, whether or not actual evidence of renal infection could be documented. It attracted little attention until the report of Spuhler and Zollinger on chronic interstitial nephritis in which they described the chronic lesion in cases other than pyelonephritis and pointed out that it was not an uncommon cause of chronic renal failure [3]. Subsequent work in this area clarified the differentiation of chronic interstitial nephritis from chronic pyelonephritis and led to the identification of analgesic abuse as a principal cause of the lesion [4].
accounted for the renal failure in 32% of the cases [6]. In the 101 patients with TIN who were reviewed, it was found that 11 were of undeterminate or idiopathic etiology, 31 had anatomic abnormalities causing obstruction of the urinary tract, 20 were due to analgesic abuse, 11 to nephrosclerosis, 9 to nephrolithiasis, one
degrees of tubular atrophy and degeneration. Glomerular
ments of tubular function and the clinical presentation are
each to sickle cell disease and tuberculosis, and 7 to multiple causes. In another study that examined this issue in a series of 363 cases of chronic renal failure, TIN accounted for 40.8% of the cases reviewed and emerged as the most common cause of renal failure. In this series, analgesic abuse nephropathy was the leading cause of TIN (32.5%), followed by obstruction Since then a motley group of diseases have come to be (19.6%), nephrosclerosis (13.5%), nephrolithiasis (8.1%), infecimplicated as a cause of chronic tubulo-interstitial nephritis. tion (1.4%), and a variety of other less common causes of TIN They have in common the altered morphologic features of the (7.4%) [7]. In both of these studies, the diagnosis of TIN was kidney and the natural course of the renal disease that develops. based on the clinical characteristics which were considered The principal morphologic features of the renal lesions are typical of TIN. One limitation imposed by this approach is that interstitial fibrosis, mononuclear cellular infiltration and varying TIN is actually a clinicopathological entity, in which derangechanges of sclerosis, atrophy and periglomerular fibrosis, while helpful in suggesting the presence of TIN, but a definite diagnosis absent initially, ultimately develop and are common features of can only be established by morphologic examination of the the end-stage kidney disease that occurs. The renal insuffi- renal tissue. Furthermore, whereas studies of the renal biopsy
ciency is slow to develop and the early manifestations of the renal involvement of these patients are those of tubular dysfunction. With progressive injury, reduction in glomerular filtration rate does occur. However, early in the course of the disease the characteristic features of glomerular dysfunction— edema, significant proteinuria, and hypertension—are absent and tubular dysfunction is almost always out of proportion to
© 1990 by the International Society of Nephrology
material have shown a close correlation of tubulo-interstitial lesions with abnormalities of renal function in an assortment of renal diseases [8, 9], there is a paucity of studies in which the morphologic findings are related to renal function in biopsy documented cases of chronic TIN. The present study was undertaken to examine chronic TIN
from a different perspective, that is, the diagnosis of TIN established by morphologic examination of renal tissue. The kidney biopsy of the cases reviewed had been performed to determine the cause of renal failure in patients presenting with
736
737
Eknoyan et a!: Chronic tubulo-interstitial nephritis
renal dysfunction on whom a definite diagnosis could not be established on clinical grounds. The study was designed to
Table 1. Morphologic features selected for semiquantitation of renal biopsy specimens
determine the clinical features present in these cases at the time
when the kidney biopsy was performed, and to examine the relation of the structural changes noted on biopsy with the degree of renal dysfunction present at the time that the renal tissue was obtained. Methods
The renal biopsy file of the Department of Pathology of Baylor College of Medicine Affiliated Hospitals was reviewed for cases coded as chronic TIN during the period covering 1971 through 1986. Eighty-four such cases were found among the 1,426 biopsies interpreted during this interval. Only 48 of these
were included in this study. The other 34 were excluded because the clinical records were incomplete or unobtainable in
9, preliminary review of the biopsies failed to confirm the diagnosis of definite TIN in 7, or the lesions noted on biopsy were those of arteriosclerosis in 20. The pathologic diagnosis of
TIN was accepted when there was predominantly chronic interstitial inflammation and interstitial fibrosis with dispropor-
tionally good preservation of glomeruli, and there was no primary glomerular or vascular disease. However, included in
the study group were four cases with primary glomerular diseases, in which the tubulo-interstitial damage was obviously severe and considerably more prominent than the glomerular lesions, rather than being obviously secondary to the glomerular lesions alone. Thus, severe TIN was present in association
Semiquantitation scales
Features Glomerular
Number of glomeruli in the biopsy Number of globally sclerotic glomeruli
Number of segmentally sclerotic glomeruli Periglomerular fibrosis
0 — 3°
Tubular
Tubular atrophy Acute tubulitis Chronic tubulitis Hyalin casts Cellular casts Interstitial Interstitial fibrosis Interstitial edema Interstitial inflammation Interstitial hemorrhage General patterns of involvement Vascular
0— 0— 0— 0— 0 — 3° 0— 0— 0— 0— d—
4b 1°
3°
p"
0 — 1° 0 — 3° 0—
Vasculitis Arteriolar thickening Arterial thickening
Abbreviations are: a 0 = absent, 1 = mild, 2 = moderate, 3 = severe; = no changes, 1 = less than 20%, 2 = 20—40%, 3 = 40—60%, 4 =
t) 0
more than 60% of biopsy surface shows the evaluated features; 0 = d absent, I = present; d = diffuse = more than 75% of biopsy surface shows changes; p = patchy = less than 75% of biopsy surface shows
with mesangial proliferative lupus nephritis (1 case), with changes. diabetic glomerulosclerosis (2 cases), and with focal segntental sclerosis in a patient with sickle cell disease. Morphological evaluation For light microscopy (LM), a portion of the biopsy was fixed
in 4% neutral buffered formalin or B5 fixative, embedded in paraffin, sectioned at 4 .tm, routinely stained with hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, and in selected cases with silver-methenamine technique. For immunofluorescent (IF) study, a portion of the biopsy was snap-
frozen, sectioned at 4 m, and stained with fluorescinated
stained with PAS was evaluated for surface area occupied by glomeruli, interstitial, vascular and tubular compartments. There was a good correlation between the morphometric and semiquantitative technique. Consequently, only the semiquantitative scores were used for correlation between morphologic, functional and clinical findings. Clinical evaluation
antibodies to IgG, 1gM, IgA, C3, C4 and fibrinogen. For electron Only cases on which adequate clinical data was available at microscopic (EM) study, the biopsy tissue blocks were fixed in the time of kidney biopsy were included in the study. The
3% glutaraldehyde at 4°, and post-fixed in osmium tetroxide. Survey sections cut at I m were stained with toluidine blue. Thin sections cut at 1 ILm were stained with lead citrate and uranyl acetate, and studied with a JOEL electron microscope (JEOL, Tokyo, Japan). LM study was done in all cases, IF in 37 cases, and EM in 38 cases. IF and EM studies, in general, did
records of these cases were reviewed, specifically for data pertinent to renal function. For purposes of this study the
diagnosis of analgesic abuse was made in patients who gave a definite history of excessive (over 1 g/day) analgesic intake prior to the onset of renal insufficiency; urate nephropathy in patients with a history of clinical gout or hyperuricemia (>9 not add significantly to the LM study, but were reviewed mg/dl) prior to the onset of renal failure; obstructive uropathy in primarily for the purpose of excluding the presence of primary patients with clinical or radiological evidence of congenital or acquired obstruction; infection was considered to be present if glomerular disease. In addition to the general LM examination, several specific the patient had repeatedly positive urine cultures in the absence features were selected for semiquantitative analysis according of other abnormalities; multiple myeloma in the presence of to the criteria outlined in Table 1. The number of sclerotic definite tissue and laboratory diagnosis of myeloma and no glomeruli was expressed as a percent of the number of glomer- other apparent cause of renal disease; sickle cell nephropathy uli available for evaluation which ranged from 6 to over 50. To on the basis of clinical and laboratory evidence of sickle validate the semiquantitative analysis, a pilot study was done hemoglobinopathy; and heavy metal toxicity from a history of on eight randomly chosen biopsies. For this purpose, the point long-term environmental exposure. Cases in which none of the counting technique utilizing a 1 x 1 cm occular reticule with 100 potential causes of TIN could be established were classified as points was utilized. The entire surface of the biopsy specimens idiopathic.
Eknoyan et al: Chronic tubulo-interstitial nephritis
738
Table 2. Clinical characteristics and diagnoses of patients with chronic tubulo-interstitial nephritis Primary diagnosis
Idiopathic Obstruction Hyperuricemia Infiltrative Analgesic abuse Arteriosclerosis Metabolic Immunologic Pyelonephritis Diabetes Totals
Serum creatinine
Sex
No. of patients
Male
8 4 6 2 4 2
12 10
6 6 4 4 2 2
Female 4 6 0 4 0 2
1
1
2
1 1
0 0 0
48
27
21
Age years
mg/dl
44.8
3.5 5.9
5.4 3.9 5.5 3.8 8.5
50.7
11.1
6.1
2.5 2.8
3 1.6
5.3
2.1
5.1
43.7 46.5
3.5 4.7
39.5 52.7
5.3
26 36 71 35
1 1
44.9
Secondary diagnosis
HTN
1.8
0.8
8 3
UTI
DM
2 5
2
UA —
1
1
1.9 1.5
6
—
1
2
2 3
1
1.0
—
0.6 2.3 12.4
1 I 1
— — — — —
0.7
26
10
1.3
OBST
— —
— — — — — —
— — — — — — — —
I — — — — —
4
1
I
I
=
— —
Abbreviations are: HTN, hypertension defined as blood pressure > 140/90 mm Hg; UTI, urinary tract infection; DM, hyperglycemia; UA, hyperuricemia of> 9 mg/dl; OBST, obstruction of urinary tract.
Statistical analysis
Table 3. Laboratory findings at the time of renal biopsy in 48 patients with chronic tubulo-interstitial nephropathy
Quantitative data, expressed as means SE, were compared
Data available
by analysis of variance (ANOVA) and by the Wilcoxon sequen-
tial rank test. Values were obtained in two-tailed fashion and considered significant if 50m1/min
them (4%) were over 70 years old. The average age of the patients was 44.9 2.1 years, for women it was 44.4 2.7
3/HPF) Pyuria (WBC's > 5IHPF) Positive urine cultures >iO organisms/mi Glycosuria Acidification defect
Percent
48 22 15
23% 26% 31%
17 19
43%
8
18%
24
11
>15 mI/mm 3.0 g/24 hr of the patients ranged from 20 to 71 years, about two-thirds of the patients (62.5%) were less than 50 years old and only two of Hematuria (RBC's >
No. of cases
44 38%
30 44
29
80% 20% 66%
44
21
48%
6
3.2 years. The lack of patients 43 28% 12 who were younger than 20 years is a reflection on the referral 44 11 25% pattern within our institution. Children and adolescents are 37 referred to a pediatric hospital, the biopsy material from which 12 32% T0 5.5 was not included in this study. The majority of the patients were Aciiification test 2 2 100% 40 27 68% white (83.3%), consisting of 66.6% caucasians, 16.6% hispan- Specific gravity < 1.015 ics, and 16.6% blacks. In 12 cases no potential cause of TIN could be established. In the remainder of cases 10 had obstruction, 6 hyperuricemia, 6 an infiltrative process, 4 analgesic abuse, 4 arteriosclerosis, 2 a metabolic abnormality, 2 an than 5.5, in the presence of acidemia (CO2
