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INTRODUCTION
It is widely held that urinary tract infection (UTI) is
more common in subjects with diabetes mellitus.
Although there are relatively few recently published
data, there is evidence suggesting that bacteriuria is
more common in females but not in males with
diabetes. Certain renal tract infections, including
emphysematous
pyelonephritis
and
cystitis,
perinephric abscess, and candidiasis, show close
association with diabetes mellitus. These, together
with renal papillary necrosis, form the basis of UTI (1).
Urinary tract is the most important and most common
site of infection in diabetic patients. Diabetic patients
have been found to have 5-fold frequency of acute
pyelonephritis at autopsy than nondiabetics (2).
The incidence of bacteriuria in diabetic men with
good control of blood sugar is reported to be similar as
in nondiabetic men, however, in pregnant diabetic
women it is 2-4 times as common as in control groups
(3,4).
Most urinary tract infections in diabetic patients are
relatively asymptomatic. The presence of diabetes
predisposes to much more severe infections, especially
in patients with poor diabetic control, acute
ketoacidosis, or diabetic complications such as
nephropathy, vasculopathy and neuropathy. This
asymptomatic infection can lead to severe kidney
damage and cause renal failure (5).
acute
recurrent
chronic
complicated
uncomplicated
85
Localization of UTI
No associated
disease
Cause of symptoms
No kidney damage
Abnormal
Normal or abnormal with
associated disease
*Diabetes mellitus
*Sickle-cell disease/trait
*Analgesic abuse
*NSAID abuse
*Stones
*Obstruction
*Vesico-ureteric reflux
reflux
*Vesicourethral
'Complicated'
calculus
obstruction
vesico-ureteric reflux
papillary necrosis
86
Impaired monocyte
function
Immune disorders (decrease in the levels of complement
/C4 / and T-helper lymphocytes) (20)
'Uncomplicated'
Normal
Impaired neutrophil
function (15-17)
calculus
scars/spongy medulla
prostatitis
foreign bodies in the urinary tract
urinary tract fistula (vesicoenteral)
congenital anomalies
Fungal infections
Viral infections
Cystitis
Invasive candidiasis *
Cystitis *
Emphysematous
cystitis *
Renal actinomycosis
Pyelonephritis
Pyelonephritis
Vulvovaginal
candidiasis *
Emphysematous
pyelonephritis*
Papillary necrosis
Perinephritic abscess
* close association with diabetes mellitus
Bacteria
Many different microorganisms can infect urinary
tract in diabetic patients, but the most common agents
of bacteria are gram-negative bacilli; Escherichia coli
causes approximately 90% of acute UTI in diabetic
patients without urologic abnormality or calculi. The
other bacilli involved, i.e. Protease, Klebsiella,
Enterobacter, Serratia and Pseudomonas, account for a
lower proportion of uncomplicated infections (26,27).
These organisms are of increasing importance in
recurrent infection of UTI in diabetic patients,
Viruses
Viruses can cause pyelonephritits in animals and may
increase the susceptibility of the kidneys to infection
with coliform bacteria (23). In humans, viruses are
most commonly found in urine samples without
evidence of acute UTI in diabetic patients, although
some adenoviruses have been implicated as a cause of
cystitis (31).
Fungi
Fungal infection of UTI in diabetic patients is
important but clinically insignificant. Diabetic patients
with urinary tract Torulopsis globrata infection account
for 20%-90% of all infections with this Candida species.
Torulopsis globrata can cause cystitis, pyelonephritis,
renal or perirenal abscess, fungus ball, and a picture of
gram-negative sepsis (33,34). The presence of candida
at a rate of >10000 colonies/m2 urine indicates
candidal infection, but diabetic patients with
indwelling catheters may have higher counts with no
significant evidence of infection by candida, which may
lead to chronic infection with severe renal damage
(29).
Tuberculosis
Tuberculosis is a serious comorbidity in diabetics, in
whom it is more extensive and 3-16 times more
common than in nondiabetics (24). The association of
UTI and tuberculosis is very common in diabetic
patients due to the impaired body defense
87
88
Description of subjects
prevalence (%)
Definition
Diabetic
Adjustment
Nondiabetic
Asymptomatic Outpatients;
Outpatients;
F:18.0
F:6.0
Bacteriuria
F:54, M:37
F:337, M:102
M:5.0
M:4.0
Bacteriuria
Outpatients;
F:18.7
F:91, M:59
F:91, M:59
M:1.7
sex distribution
M:3.3
None
Diabetic
Nondiabetic
Bacteriuric
(%)
Women
54
337
20
91
19
19
114
11
100
81
18
81
44
16
27
15
341
100
5
2
91
128
97
18
Men
OSullivan et al. (1961)
59
59
Vjelsgaard (1966a)
141
146
97
11
100
67
67
37
102
411
100
89
Pathogens
Escherichia coli is the most common organism isolated.
Schmitt et al. (47) found it to account for 75% of
isolates from female diabetics. There is no significant
difference in bacterial isolates between diabetic and
control subjects, although bacterial counts are generally
higher in the former (6). Group B streptococcus is said
to be more common in diabetic subjects with
pyelonephritis (59).
Therapy
Positive urine cultures (i.e. >10 organisms/ml) should
be treated in diabetic individuals even if
asymptomatic. The choice of antibiotic should reflect
the sensitivity of the organism, and treatment does not
differ between diabetic and nondiabetic individuals,
although some authors prefer longer duration of
treatment in diabetic patients (63). A 14-day course of
90
Conclusion
INFECTIVE TUBULOINTERSTITIAL
NEPHRITIS
This poorly recognized cause of infection and
occasionally of acute renal failure in unobstructed
kidneys was initially documented in two series by
Richet and Mayaud (1978) in 30 cases (67), and by
Baker et al. (1979) in five cases (68). The larger series
included histologic evidence for an acute infection with
microabscesses. The condition was reviewed by Cattell
(1992) (69). From the published series it appears that
diabetes is a risk factor for acute renal failure in this
group (69,70), along with analgesic abuse, nonsteroidal drug use, sickle-cell disease (or trait), and
possibly alcoholism.
ACUTE RENAL FAILURE
Although definite data are lacking, there is an
impression that diabetic patients may be more likely
than nondiabetics to suffer renal failure as a result of
UTI and subsequent pyelonephritis and septicemia.
Apart from infective tubulointerstitial nephritis
described above, this may result from the failure of
autoregulation of renal blood flow with falls in blood
pressure in patients with even moderate degrees of
diabetic nephropathy (71).
RENAL TRACT CANDIDIASIS
Diabetes appears to be more common in individuals
with fungal UTI. It is present in up to 90% of patients
with Candida glabrata (formerly Torulopsis glabrata)
(72,73). Candida albicans was cultured from the urine of
91
Clinical presentation
The presentation of RPN may be acute or chronic. The
former may be fulminant with flank pain, fever and
septicemia. It is generally unilateral. Papillae may
slough, leading to renal colic. The affected kidney may
be enlarged (94). The chronic indolent form is more
commonly observed. Here changes are often bilateral.
Unilateral papillary necrosis suggests the presence of
renal artery stenosis or atrophy associated with
previous ureteric obstruction. The changes in the
kidney may be patchy with the papillae exhibiting
differing degrees of necrosis.
RPN is most usually seen in the 6th and 7th decades of
life (93), women being more often affected than men
(3:1) (95). Microscopic hematuria is a common finding,
occurring in 44% of diabetic subjects with RPN (89). A
previous history of UTI was found in 68% of cases (89).
Renal insufficiency develops in 15% (96). The
diagnosis should be suspected in a subject with UTI
who responds poorly to antibiotics, or develops
unexplained renal failure (95).
92
Introduction
The presence of gas in the renal tract is relatively
uncommon but shows strong association with diabetes
mellitus. Pneumaturia was first described as early as
1671 (cited in Taussig, 1907) (100), but this and
subsequent observations often failed to specify the
origin of gas, which may arise in three ways:
1) prior instrumentation,
2) vesicocolic or vesicovaginal fistula, and
3) spontaneous gas formation in the bladder.
Raciborski (1860) (101) is credited for the first
description of spontaneous gas formation. An earlier
much quoted case described by Brierre de Bosmont
(cited in Kelly and MacCallum, 1898) (102) is open to
doubt.
The link with diabetes mellitus was recognized early
by Guiard (1883) (103) who described four cases of
pneumaturia in association with glycosuria. The first
substantive literature review by Kelly and MacCallum
(1898) (102) reports on 9 of 16 cases of pneumaturia to
have glycosuria. The validity of some of these cases is
questioned by Turman and Rutherford (1971) and
Zabbo et al. (1985) (104,105).
The classification of emphysematous renal tract
disease (ERTD) presents a problem. That of Turman
and Rutherford (1971) (104) is most logical and
comprehensive (Table 3). However, some of these
(e.g., emphysematous ureteritis) may not exist as
distinct entities, whilst two or more, such as
emphysematous pyelonephritis and perirenal gas may
occur in combination. It is proposed to concentrate on
the three conditions most commonly seen, i.e.
emphysematous pyelonephritis with perirenal gas,
emphysematous pyelitis, and emphysematous cystitis.
All early descriptions of pneumaturia where a fistula
was excluded probably referred to emphysematous
cystitis, as emphysematous pyelonephritis rarely gives
rise to this symptom.
The pathogenesis of ERTD is incompletely
understood. Early theories (106) that the gas, usually
CO, although N, H, O and CH (methane) are also
present, is a product of glucose fermantation, still hold
today (107,108). Obstruction, and perhaps diabetic
Outside of
renal tract
Tissue
Kidney
Emphysematous
pyelonephritis
Perirenal gas
Pelvis
Intrapelvis gas
Emphysematous
pyelitis
Ureter
Intraureteral gas
Emphysematous
ureteritis
Periurethral gas
Bladder
Intracystic gas
Emphysematous
cystitis
Pericystic gas
Emphysematous pyelonephritis
It is defined as the presence of gas in renal
parenchyma and is often associated with perirenal gas.
It is a severe life-threatening necrotizing infection with
a mortality in excess of 60%. No substantive series of
this condition exists, although there are some literature
reviews (111-113).
Clinical features
Ninety percent of cases of emphysematous
pyelonephritis are associated with diabetes mellitus
(113), although no breakdown of the type of diabetes is
given. The mean age reported is 54 (range 19-81) years,
and women are affected twice as often as men. In
contrast to earlier findings that the left kidney was
more commoly affected (112,114), a more recent
survey (113) found no difference. Bilateral
involvement in association with diabetes has been
described in rare cases (105,115,116), and in several
cases in transplanted patients (117-119).
The clinical presentation is often suggestive of severe
acute pyelonephritis, but it may also have an indolent
course over several months. In 43 cases the average
duration of symptoms was 21 days, ranging from less
than a day to eight months (112). Nausea, vomiting
(40%) and abdominal pain (55%) are common
symptoms. Fever is seen in 80% (113). A palpable mass
Laboratory investigations
Neutrophil leukocytosis is observed in the majority of
cases. Pyuria is found in 96% (113). Pre-existing renal
function was abnormal in 82% of 36 subjects (112).
Microbiologic investigation shows Escherichia coli to be
the most common causative organism. In one series,
68% of cases were due to this organism and 9% due to
Klebsiella (120). Multiple organisms were found in 14%.
Other organisms are rare and many are reported as
single cases. Candida albicans (105), Candida tropicalis
(121), cryptococcus (116), and anaerobic streptococcus
(43) have been recorded. Clostridium spp. has not been
described (112). Pathologic examination of the tissue
will often reveal an acute inflammation of the
interstitium with multiple micro- and macroabscesses.
Diagnosis
Renal tract emphysema is a radiologic diagnosis as the
symptoms and signs are a little different from other
renal infections. The diagnosis should be suspected in
any diabetic patient with nausea, vomiting and
abdominal pain, particularly where antibiotic therapy
fails to improve an acute pyelonephritis in three to
four days. Plain abdominal x-ray or IVU will reveal gas
in 50%-80% of cases (112,113). Contrast studies should
be used judiciously in diabetic subjects with impaired
renal function. Langston and Pfister (1970) (122)
describe radiologic features of emphysematous
pyelonephritis and highlight three patterns. An initial
mottling with gas in the renal parenchyma is followed
by the development of a crescent of gas surrounding
the parenchyma. Finally, extravasation of gas occurs
through Gerotas fascia into the retroperitoneal space.
Such x-ray features are, however, seen in relatively few
cases. A simplified classification is suggested by
Michaeli et al. (112):
stage 1: gas in the renal parenchyma or perirenal tissue
stage 2: gas in the kidney and surrounding tissues
stage 3: extension of gas through Gerotas fascia
Where there is some doubt, or where delineation is
important, the patient should have a CT scan.
93
Emphysematous pyelitis
In this condition, gas is limited to the collecting
system. Evanoff et al. (113) found the condition to be
more common in women (3:1), with an overall mean
age of 51 (range less than one to 79) years. In contrast
to emphysematous pyelonephritis, only 59% of subjects
had diabetes, presumably due to a higher proportion of
patients with obstruction in this group (64% vs. 37%).
For reasons that are not clear the left kidney was
affected more commonly than the right one (53% vs.
36%), and bilateral gas was rarely observed (125).
The total number of cases is not documented. The
symptoms are similar to those in emphysematous
pyelonephritis. Escherichia coli is again the most
common organism. Radiology reveals gas in the
collecting system. US or IVU may demonstrate an
obstruction. Gas occurs rarely in the bladder in
association with emphysematous pyelitis (124).
Histopathologic studies in this condition show acute
inflammation with submucosal hemorrhage of the renal
pelvis and ureter. Renal parenchyma may show an acute
interstitial reaction (127).
Treatment for this condition includes antibiotic
therapy with relief of obstruction where necessary. The
reported mortality is 18% (113).
Conclusion
ERTD, although uncommon, may be associated with
a high mortality. Many cases are associated with
diabetes mellitus. A high index of suspicion,
appropriate radiologic assessment, and early surgical
intervention offer the best hope for cure in
emphysematous pyelonephritis. Emphysematous
pyelitis and cystitis are more benign and are treated
with antibiotics alone or a combination of antibiotic
and relief.
Emphysematous cystitis
94
IVP - Intravenous
pyelography
Micturition
cystogram
Children 4 years
Children 4 years
Recurrent infection
Women with
bacteriuria
IVU suggestive of
urinary obstruction
Women with
cystitis
Rarely helpful
Women with
acute
pyelonephritis
Rarely helpful
Men diabetic
IVU of shows
abnormality
Consider early of
symptoms of
recurrent onset
Rarely helpful
High risk
patients
High obstruction
urolithiasis, persistent
pyuria
Rarely helpful
Outpatients (134,135):
frequent glycemic control (at 4-hour intervals)
higher insulin dose for correction of
hyperglycemia
sufficient liquid intake
consultation with a diabetologist/nephrologist
urgent hospitalization in case of: vomiting
development of hyper- or hypoglycemia
Inpatients (134,135):
frequent glycemic control (at 2-hour intervals)
higher insulin dose for correction of
hyperglycemia
- intravenous rapid acting insulin when
required
starting insulin therapy in patients on oral
therapy
95
96
Dose (mg)
Nitrofurantoin
50
Trimethoprim
100
Norfloxacin
200
Ciprofloxacin
125
Cephalexin
125
(useful if renal insufficiency)
97
REFERENCES
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100
101
Am
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103