Changes in urine volume
• Polyuria: >3L/24h.
• Oliguria: <400mL/24h.
• Anuria: <100mL/24h.
Polyuria
Excretion of a urine volume in excess of normal; >3L/day is an arbitrary cut-off. H 2 O excretion is tightly controlled, so daily volumes vary widely in an individual.
It is usually frequency of micturition (especially overnight) s to the larger volume, rather than the volume itself, that causes the patient to pre-sent (although most patients with frequency do not have polyuria). Obtain a 24h urine collection for volume before undertaking further investigation.
Polyuria is seen in three clinically important situations (see Table 1.14):
• Excessive fl uid intake.
• Increased tubular solute load, e.g. hyperglycaemia.
• Failure of the renal tubules to concentrate the urine (diabetes insipidus, b p. 789).
Table 1.14 Conditions associated with polyuria
i Fluid loss
Renal tubular Nephrogenic diabetes insipidus, acquired tubular defect (e.g. caused by pyelonephritis, post-obstruction, chronic d K + , i Ca 2+ ), nephrotoxins (e.g. aminoglycosides, cisplatin, lithium), diuretics, Bartter ’ s syndrome, polyuric recovery phase of AKI
Endocrine Central diabetes insipidus, Addison ’ s disease, hyporeninaemic hypoaldosteronism Osmotic diuresis Glycosuria, mannitol, contrast agents i Fluid intake
Psychological Psychogenic polydipsia
Oliguria
Passage of a urine volume inadequate for excretion of the end products of metabolism. <400mL/24h ( 7 20mL/h). The causes of oliguria (and anuria) are analogous to those of AKI.
Anuria
Passage of <100mL/24h or the absence of urine fl ow.
2 Address the following questions urgently if anuria:
1. Is the bladder catheter blocked?
2. Is the urinary tract obstructed?
3. Are the kidneys perfused?
CLINICAL SYNDROMES: URINE VOLUME AND URINARY TRACT PAIN 75
Pain Loin pain
• Renal pain is usually experienced in the loin near the costovertebral angle.
• Anterior radiation may cause confusion with intraperitoneal pain.
• May also radiate to the genitalia.
• Usually associated with distension of the renal capsule and described as a constant dull ache.
• Differential: nerve root irritation (commonly T10 – T12).
• 2 An aggressive and a destructive renal disease may be painless.
Ureteric colic
• Sudden onset, extremely severe (pale, distressed, unable to settle) colic.
• Caused by a combination of ureteral stretching, local infl ammation, and hyperperistalsis (spasm of ureteral smooth muscle).
• Pain may not completely fade between exacerbations.
Causes
• Passage of a stone (common), blood clot, or sloughed papillae.
• Ureteral pathology that develops slowly or produces only partial obstruction may be painless (small stone l excruciating colic; large, non-obstructing staghorn calculus l no pain).
• Pattern of referred pain can sometimes help to determine the level of ureteric obstruction:
• Upper ureter l loin
• Mid-ureter l ipsilateral iliac fossa (may l testicle in ♂ , labium in
♀ , and upper thigh in both).
• Lower ureter l bladder irritability (frequency, dysuria, urgency) and suprapubic discomfort (may l urethra and tip of penis).
The bladder Suprapubic pain
• Usually overdistension of the bladder (acute retention) or local infl ammation (cystitis).
• Cystitis: signs of bladder irritability (below) and sharp, stabbing pain towards the end of voiding (strangury).
• Slowly progressive distension (e.g. neurogenic bladder) may cause no pain.
• Constant suprapubic pain, unrelated to retention, may not originate in the bladder. In ♀ , consider gynaecological causes.
Bladder irritability
• Dysuria, frequency, and urgency among the commonest symptoms encountered in clinical practice.
• Urinary infection, causing infl ammation of the urethra, trigone, and bladder, is (by far) the most frequent cause ( b p. 706).
• About one-third of patients with bladder cancer present with bladder irritability.
Clinical syndromes: tubular syndromes
Introduction
A degree of tubular dysfunction may occur with any renal injury (though the clinical picture is usually dominated by d GFR). Several distinct clinical syndromes result from tubular defects in the context of a normal GFR.
Generalized tubular dysfunction (Fanconi syndrome) Multiple tubular defects produce a distinct clinical phenotype referred to as the Fanconi syndrome (unrelated to Fanconi ’ s anaemia). Components may be present to a variable degree.
Causes
• Acquired: drugs (aminoglycosides, sodium valproate, ifosfamide, nucleoside reverse transcriptase inhibitors) and toxins (ethanol, cadmium, uranium, lead, mercury), myeloma, SLE, Sj ö gren ’ s. Mild forms of the syndrome are more common than was previously thought.
• Inherited: cystinosis, tyrosinaemia, fructose intolerance, galactosaemia, glycogen storage disorder type I, cytochrome c oxidase defi ciency (all autosomal recessive). There is also an autosomal dominant idiopathic form of Fanconi syndrome. Dent ’ s disease and Lowe syndrome are X-linked Fanconi-like disorders.
Features
• Phosphaturia and bone disease:
• Impaired PO 4 reabsorption l phosphaturia l hypophosphataemia.
• This, and impaired 1 A hydroxylation (activation) of
25-hydroxyvitamin D 3 in proximal tubular cells, produces skeletal abnormalities, including rickets (children), osteomalacia (adults), and osteoporosis.
• Aminoaciduria:
• Amino acids are usually fi ltered at the glomerulus before reabsorption by multiple transport carriers in the proximal tubule.
• Fanconi syndrome l all amino acids appear in the urine in excess.
• No clinically signifi cant sequelae and supplementation unnecessary.
• Glycosuria:
• Amount varies but serum glucose usually normal.
• Clinical sequelae are rare, though hypoglycaemia occurs in some forms (e.g. Fanconi – Bickel syndrome/glycogenosis).
• Renal tubular acidosis (RTA):
• Defective bicarbonate reabsorption in the proximal tubule results in systemic acidosis (a form of type II RTA, b p. 824).
• Na + loss:
• If severe l postural d BP, d Na + , and metabolic alkalosis result.
• Salt supplementation occasionally necessary.
• Hypokalaemia:
• i delivery of Na + to the distal tubule l Na + reabsorption at the expense of K + excretion.
CLINICAL SYNDROMES: TUBULAR SYNDROMES 77
• Acidosis and RAS activation by volume depletion also l K + loss.
• Clinical sequelae common (muscle weakness, constipation, polyuria, cardiac arrhythmias) and supplementation often required.
• Proteinuria:
• LMW proteinuria is common ( B 2 microglobulin, lysozyme, and other tubular proteins), though excretion rates are usually low – moderate.
• Polyuria:
• Polyuria, polydipsia, and dehydration can be prominent.
• Caused by d K + and impaired concentrating ability in the distal tubule.
• Hypercalciuria:
• Rarely l nephrolithiasis/calcinosis (? protective effect of polyuria), although these may be precipitated by treatment with vitamin D metabolites (further i urinary Ca 2+ ).
• Serum Ca 2+ usually normal.
Isolated tubular defects Renal glycosuria
• d proximal tubular glucose reabsorption l glycosuria (despite normal blood glucose).
• Clearance studies allow differentiation into different patterns implicating several defective tubular transport mechanisms.
• The amount can be quite signifi cant (normally 1 – 30g/24h) but generally a benign condition with no clinical sequelae.
• Always needs to be distinguished from DM.
• Genetic mechanisms involved but inheritance unpredictable.
Aminoaciduria • Causes:
• Inborn error of metabolism l i plasma levels and ‘overfl ow ’ . • Renal aminoaciduria secondary to defective tubular transport
mechanisms.
• Amino acid transport is complex, involving transporters specifi c to single or chemically related groups of amino acids.
• The most important isolated aminoaciduria is cystinuria, an autosomal recessive cause of recurrent cystine stone formation ( b p. 719).
Phosphaturia
• Defective phosphate transport l phosphaturia, hypophosphataemia, and disorders of the skeleton.
• Several described, including X-linked hypophosphataemic rickets (vitamin D-resistant rickets) and autosomal dominant hypophosphataemic rickets.
• FGF-23 excess, causing inhibition of phosphate reabsorption, is now known to underpin many of these disorders ( b p. 236).