mecha-

nism between the ureter and the bladder (the

vesicoureteric   junction;   Figure 14.20),   Vesi-

coureteric reflux leading to reflux nephropathy usually starts in infancy, and may stabilize or

progress slowly to CRF in adulthood.

In bladder outflow obstruction, e.g. prostatic hypertrophy, urinary retention may be accom-

modated   by   bladder   distension,   with   little serious rise in intrarenal pressure.

Aetiology

The commonest causes of obstruction are listed

in Table 14.22. In the West, the most frequent

causes are gynaecological problems in women,

prostatic hypertrophy in men, and stones in

both.

Renal calculi (urolithiasis)

The lifetime prevalence of renal stones is about

10% in males and 5% in females, although not

all cases are symptomatic. The causes are poorly

understood. Calcium oxalate stones, the most

common type, may result from hypercalciuria

(high   urinary   calcium)   or   excessive   gastro-

intestinal absorption of oxalate (hyperoxaluria).

Stone formation is encouraged by an alkaline

urine,  e.g.  from  renal  tubular  acidosis,  and

hyperuricosuria, e.g. in hyperuricaemia or gout

(Chapter           12).      Conversely,    hyperuricaemia

together with an acid urine predisposes to urate

stones. In urinary infections caused by urease-

producing organisms, especially Proteus spp., the

urinary alkalinity and ammonium content cause

co-precipitation   of   mixed   phosphate   stones

(calcium,   magnesium   and   ammonium).   In

cystinuria, an inherited metabolic disorder, the

reduced tubular reabsorption of cystine results in

high urinary levels and cystine stone formation.

Clinical features and investigation

Symptoms  depend  on  whether  the  lesion  is

above or below the bladder outlet. In the latter

case,  dysuria,  hesitancy,  frequency,  terminal

dribbling or bladder distension and discomfort

occur. Above-bladder obstruction usually causes

renal   colic (sudden   severe   and   debilitating

unilateral loin pain due to ureteric spasm) often

associated   with   haematuria   and   complete

ureteric obstruction. Colic is also caused by the movement of stones in the ureter.

The urine flow disturbance will also depend on

the degree and site of obstruction and whether it

is bilateral. Paradoxically, polyuria may occur,

owing   to   tubular   damage.   Chronic   reflux

nephropathy, caused by bladder contents being

refluxed into the renal pelvis, may result in

hypertension   and   recurrent   renal   infection

(pyelonephritis).

Investigation ranges from simple examination and   analysis   of   the   urine   to   sophisticated imaging and biopsy.

Management

Whereas surgery used to be common in treating

obstruction, conservative management is increas-

ingly used, owing to the growing appreciation

that renal function may be preserved or restored,

and to the development of techniques of percuta-

neous  intrarenal  manipulation.  Surgical  repair

may be essential in some cases, e.g. a congenital

defect, but nephrectomy is now quite rare.

Small  stones  (especially  cystine)  may  be

passed in the urine if output is encouraged by

ample  fluid  intake (more  than 3L  daily),

especially  overnight.  Antispasmodics  such  as

propantheline    (contra-indicated   in   bladder

outflow obstruction) or catheterization may also

assist  the  passage  of  stones.  Penicillamine  will

help  to  dissolve  cystine  stones.  Reducing

urinary urate levels with allopurinol may help.

Alkalinization of the urine, e.g. with potassium

citrate mixture, will also reduce hypercalciuria

and in turn the formation of both urate and

cystine stones. Urinary acidification, e.g. with

ammonium  chloride,  will  minimize  phosphate

stone production.

For  oxalate  stones,  sodium  restriction  and thiazides are used both to reduce urinary calcium (thiazides   promote   tubular   reabsorption   of calcium) and to increase urine flow. It is impor-

tant not to reduce dietary calcium in an attempt to treat hypercalciuria, because, paradoxically, this tends to increase future stone formation and also cause loss of calcium from bones.

Nephrostomy may permit extraction of larger

pelvic stones and drainage in hydronephrosis.

Stones may be ultrasonically disrupted by extra-

corporeal shock-wave lithotripsy (ESWL) and the

fragments passed out in the urine. Fibre-optic

ureteroscopy, which requires general anaesthetic,

may be required. Open surgery is rarely necessary.

In reflux nephropathy prompt treatment of

infections and adequate control of hypertension are likely to prevent progression. Surgery is rarely indicated, except for reconstruction of a congen-

itally abnormal vesicoureteric junction.

Renal colic is treated with either pethidine or,

increasingly,   an   NSAID        (diclofenac),   which

reduces ureteric spasm in addition to its anal-

gesic effect. IV fluids are used to promote urine

flow, especially as the patient is likely to be

extremely nauseous.

In   all   methods   employing   treatments   to encourage urine flow, it is of course important to ensure  initially  that  there  is  not  complete

obstruction.

Infection

As with obstruction, there is a significant differ-

ence between infections of the lower and upper

renal systems. Lower urinary-tract infection (e.g.

urethritis, cystitis) causes discomfort, inconve-

nience and not a little pain, but is essentially

benign if restricted to a single attack at that site.

Conversely,   infection   of   the   kidney (upper

urinary-tract   infection   or   pyelonephritis)   is

always serious and has systemic complications. It

may   even   lead   to   CRF:   indeed,   chronic

pyelonephritis accounts for some 10% of all

ESRD.

However,    urinary-tract           infection            and

pyelonephritis are not completely distinct. Most

kidney infections are presumed to have ascended

from asymptomatic, untreated or inadequately

treated urinary-tract infection, and this retro-

grade infection is encouraged by the urinary

stasis,   which   can   result   from   obstruction.

Repeated or serious urinary-tract infection can

itself  lead  to  obstruction  by  causing  ureteric

fibrosis and stricture (narrowing). The patholog-

ical spectrum, from asymptomatic bacteriuria to

what is still termed chronic pyelonephritis, is

illustrated in Figure 14.21.

Because pyelonephritis causes inflammatory

damage there is also some pathological similarity

to such conditions as nephrotoxicity, analgesic

nephropathy, reflux nephropathy and the renal

manifestations  of  connective  tissue  disorders,

e.g. SLE. The generic term interstitial nephritis is

often preferred.

Urinary-tract infection

Because of the close pathogenetic links between

urinary-tract   infection,   reflux   nephropathy,

obstruction  and  pyelonephritis,  some  of  the

general features of urinary-tract infection are

discussed  here  so  as  to  present  a  complete

picture of renal system infections. Full details of

urinary-tract infections, especially their investi-

gation and management, are given in Chapter 8.

Aetiology and pathology

Urine is normally sterile. The faecal commensal

Escherichia coli is responsible for acute infection in

75% of those cases where a urinary organism is

identified.  Less  common  pathogens  include

staphylococci,  faecal  streptococci,  Proteus  and

Klebsiella.  Non-specific  urethritis        (i.e.  non-

gonococcal) is usually caused by Chlamydia spp.

Women.   Even   with   the   strictest   hygiene,

urinary-tract contamination with skin commen- sals or faecal organisms is difficult to avoid in

women. This is due to the anatomical proximity

of the urethral and anal openings, and the rela-

tively short urethra. Simple urinary-tract infec-

tion is far more common among women than

men.

The   route   of   infection   may   be   anus-

vagina-vulva-urethra. Vaginal secretions, urine

and the urinary tract all normally have protec-

tive antimicrobial properties, e.g. mucosal IgA,

locally acidic pH, frequent flow. Thus, recurrent

infection suggests a breakdown in these defence

mechanisms,  e.g.  obstruction,  or  a  protected

focus of infection, e.g. infected stones. Persisting

vaginal organisms may be introduced into the

urethra  mechanically,  especially  during  inter-

course -  hence  the  rather  quaint  but  now

distinctly   anachronistic   term   ‘honeymoon

cystitis’. Urinary-tract infection is more common

among postmenopausal women owing possibly

to a loss of protection afforded by oestrogens.

Although bacteriuria is found in about 5% of

adult women, few of these suffer symptoms.

Such asymptomatic or covert bacteriuria gener-

ally does not require treatment except during

pregnancy,  where  there  is  a 30%  chance  of

progression to acute pyelonephritis due to intra-

abdominal ureteric compression. On the other

hand, no organism can be found in up to 50% of

women who do have symptoms of cystitis; this is

known   as   abacterial   cystitis             (or        ‘urethral

syndrome’).

Men.   Infection in males is much rarer and

always  requires  investigation.  Sexually  trans-

mitted   non-specific   urethritis   is   the   most common cause in young men and chronic bac-

terial prostatitis in older men.

Both sexes.   In the elderly of either sex the

prevalence of urinary-tract infection may rise to 30% and this is a particular problem in institu-

tions. Catheterization alone carries a risk of infec-

tion variously estimated at between 2% and 20%. In diabetics, reduced host defence and glycosuria predispose to urinary bacterial growth.

Clinical features and course

The hallmark of acute urethritis/cystitis is an

intense burning sensation on micturition, to

which the simple term dysuria fails to do justice.

The condition may be exacerbated by a more

acid urine resulting from local bacterial metabo-

lism. Urinary frequency is common and there

may be suprapubic pain or discomfort. Pyuria,

purulent discharge or even haematuria may also

occur  but,  although  alarming  and  requiring

investigation, are not necessarily sinister. There

are no systemic signs. The elderly commonly

present with acute confusion, fever, malaise or

anorexia  but  few  specific  urinary  symptoms,

making it easy to miss during examination. It is

also difficult to spot in young children if not

suspected.

Urinary-tract infection is usually self-limiting within a few days, especially if fluid intake is promptly increased substantially. It may have no complications in the absence of any other renal abnormality. However, recurrence is common owing   either   to   infection   with   a   different organism, or to relapse or re-infection with the same organism. The latter situation suggests the presence   of   a   complicating   factor   that   is preventing complete eradication.

Investigation

Two  things  must  be  determined:  (i)  which

organism is responsible; and (ii) are there any

underlying causes or correctable complications?

The collection of urine samples and the indica-

tions for further investigation are discussed in

Chapter 8.

Management

In the management of urinary-tract infection

the aims are to:

•  reduce the risk of renal damage. •  provide symptomatic relief.

•  render the urine sterile.

•  provide prophylactic therapy.

The first of these is achieved by prompt atten-

tion and full investigation when appropriate.

General measures include increasing the fluid

intake substantially to promote urine flow, and

providing advice on hygiene. For women, advice

includes front-to-back wiping after defaecation

(although the role of this has been disputed),

and micturition before and after coitus. Frequent

recurrence or relapse in the absence of obstruc-

tive  or  other  correctable  complications  may

require prophylactic therapy. For details of treat-

ment, see Chapter 8.

Acute pyelonephritis

Like lower urinary-tract infection, most cases of acute pyelonephritis (APN) occur in women. E. coli  is the usual culprit, but Proteus, Staphylo-

coccus   and   Pseudomonas   are   found   more commonly than in simple urinary-tract infec-

tion. Tubular inflammation causes polyuria and a dilute urine but severe cases may progress to acute oliguric renal failure.

Clinical features

An acute onset of severe loin pain is accompa-

nied by systemic features such as fever, nausea

and vomiting. There may also be lower urinary-

tract   infection   symptoms   of   cystitis   and

urethritis (Figure 14.20). Rarely, if both kidneys

are affected, tubular oedema and inflammatory

exudate may cause intrarenal obstruction with

acute post-renal failure.

Management

Prompt appropriate oral antimicrobial therapy and an increased fluid intake are always indi-

cated. The same agents are used as in urinary-

tract  infection.  However,  close  attention  to microbiological results is vital because of the

greater likelihood of unusual or resistant organ-

isms and the importance of characterizing recur-

rence as either relapse, i.e. the same organism, or re-infection possibly with another.

Most  patients  have  a  single  attack  of  APN

and  recover  completely,  but  recurrent  attacks

or  persistent  asymptomatic  bacteriuria  require

further  investigation.  If  the  recurrence  is  a

relapse  with  the  same  organism,  either  the

antimicrobial   therapy   was   inadequate   or

there may be obstructive/reflux abnormalities.

Frequent re-infection with different organisms

or  strains  suggests  that  the  host  defences  are

defective,  and  that  prophylactic  antimicrobial

therapy  should  be  considered.  This  can  be

continuous  low-dose  therapy,  or  intermittent

5-day  full-dose  courses  at  the  onset  of  symp-

toms, which the patient can be instructed to

initiate.

Reflux nephropathy (chronic pyelonephritis)

Definition

The term chronic pyelonephritis has traditionally

been used to describe a condition diagnosed radi-

ologically where one or both kidneys appear irreg-

ular,  shrunken  and  scarred.  However,  because

evidence is accumulating of a strong association

with  reflux  or  infection,  the  term  reflux

nephropathy is now preferred. Although most

cases do not progress to renal failure, it can be

extremely difficult to treat, and renal scarring is

present in up to 20% of patients starting dialysis.

Pathogenesis

The relative contributions of chronic infection

and  sterile  reflux (causing  simple  pressure

damage) are still uncertain. Many patients have

neither bacteriuria nor a history of urinary-tract

infection, and although urinary-tract infection

and  APN  are  far  more  common  in  women,

reflux  nephropathy  shows  equal  sex  distribu-

tion. One form may result from vesicoureteric

reflux starting in the very young, and this has a

poorer  prognosis  because  it  may  be  silent  or

undiagnosed for long periods. In adults, recur-

rent  urinary-tract  infection  or  APN  may  be

responsible.

Bacterial   reflux   nephropathy   commonly

involves  more  virulent  Gram-negative  organ-

isms,  including  Pseudomonas,  and  persistent

infection with relapses is common. In contrast to

the urinary tract the renal pelvis seems to have

no natural antibacterial defences (presumably

evolution never anticipated organisms there).

There may even be factors that encourage the

microbial persistence, so complete eradication is

difficult.

Clinical features and investigation

The condition may be asymptomatic or may

present as proteinuria, hypertension or recurrent

urinary-tract infection. Rarely, the first indica-

tion may be symptoms of incipient renal failure

Important renal diseases            935

such as polyuria or nocturia, because the renal

damage is primarily tubular. Early reflux damage

may   initiate   the   hypertension-renal   failure

vicious cycle, and sometimes a history of related

childhood illnesses such as enuresis or cystitis

may  be  traced.  Diagnosis  and  investigation

involve urography, urine microbiology and renal

function tests.

Management

In the absence of renal impairment, all that may

be required is regular monitoring of blood pres-

sure,  urine  microbiology  and  renal  function.

Infective episodes must be treated promptly as

for APN, and appropriate antimicrobial prophy-

laxis may be indicated if bacteriuria cannot be

eliminated. In children, surgery to correct reflux

may be necessary.

Course and prognosis

Most patients have stable disease, especially if their BP and bacteriuria are managed success-

fully. Recurrent infective exacerbations carry a poorer prognosis, but only about 1% of patients progress to CRF.

Glomerular disease

Glomerular   disease   invariably   affects   both kidneys. Glomeruli seem especially sensitive to inflammatory immune damage, and most forms of  glomerular  disease  involve  immunological mechanisms.  Glomerulonephritis (GN)  is  the single most important cause of CRF.

Classification

For such a small and apparently simple structure

the glomerulus presents inordinate pathological

complexity. Descriptions of glomerular disease

have a long history in medicine, and under-

standing of the condition is confounded by the

numerous methods of classification. Moreover,

increasingly   sophisticated   microscopy   and

immunological techniques continue to identify

new criteria and subgroups. Thus, in addition to simple  clinical  and  aetiological  classes  there are histopathological and immunopathological groupings (Table 14.23).

There  is  no  consistent  correlation  between

these  different  methods  of  classification  and

much overlap. No single classification provides

an  unequivocal  guide  to  management,  and

usually each aspect needs to be specified