A 69 yr old obese lady, is noticed to be passing very little urine (164mls in 24 hrs). She is 3 days post operative following MUA and k-wiring  of  a fractured right distal radius. A day after surgery she had developed a very swollen and painful right knee which the house officer on call had treated as a septic arthritis, with i.v. flucloxacillin, oral fusidin and diclofenac. She has a past medical history of osteoarthritis, hypertension, hiatus hernia and diverticular disease.                                                                                                                     

Investigations

Hb 9.8; ; WCC 5.8 ;  platelets 260; MCV 92

Na+  141; K+ 4.1; Urea 28; Creatinine 532; Creatinine kinase 1042;

Clinical approach

It is quite clear that this patient has either acute or acute- on- chronic renal failure which can only be distinguished on the basis of the urea and electrolytes at the time of admission. (hence the need for a baseline of investigations on admission of every patient)

The problem we have here is in identifying the cause of acute renal failure on which management depends. As in all cases, there is no substitute for a detailed history and good clinical examination.

History of the presenting problem

Establish whether the patient had pre-existing renal failure:

-What was the serum creatinine on admission?

-Has she ever had kidney problems before?

Leads that need to be followed in this case include:

-How did she sustain the fracture? Is there a possibility of extensive soft tissue injury? (rhabdomylosis)

-Drug history- ask about prescribed and non-prescribed drugs e.g NSAIDS( vasoactive effect, tubulointerstitial nephritis, papillary necrosis), Aminoglycosides ( tubular toxicity), ACE inhibitors and AII blockers (vasoactive effect), penicillins (interstitial nephritis)

-Over- the- counter  or HERBAL MEDICINES

-Recent angiogram or IVP (contrast nephropathy from nephrotoxic dye)

- Urinary (prostatic) or gynaeclogical symptons (obstruction)

-Family history of renal disease (Alport’s syndrome, autosomal dominat polycystic kidney disease)

- Inquire about systemic symptoms such as joint pain, rashes or fever (suggesting vasculitis or connective tissue disease)

-Find out about backache or bone pain (myeloma, metastic prostate cancer)

- Chest pain/angina ( perioperative myocardial ischemia or infarction, arteriopathy)

-Diabetes, hypertension

Examination

-Vitals: BP (standing/sitting and recumbent), pulse, respiratory rate, oxygen saturation and temperature, should all be determined within minutes of seeing the patient.

-Assess fluid balance (more info)

- Look for rashes (vasculitis, cholestrol embolisation)

-Facial appearance (sclerodema, butterfly rash of SLE)

-Heart murmurs (infective endocarditis)

-Pericardial rub (a consequence of uremia)

-A palpable bladder is an indication of bladder outflow  obstruction, and should be followed by a rectal and pelvic examination.                        

-Perform fundoscopy (accelerated hypertension)

Investigations

Three simple tests, often forgotten, are:

-Urine dipstick: The prescence of blood and proteinuria is highly suggestive of glomerulonephritis or vasculitis. Their absence almost excludes it-you need to know this now

If urine dipstick is positive for blood but with no red cells visible on urine microscopy, this suggests rhabdomyolosis-confirmed by measurement of serum creatinine kinase ( our patient had a high CK )

-Urine microscopy:  The presence of red cell casts indicates renal inflammation caused by acute glomerulonephritis (of various types), renal vasculitis (of various types), accelerated-phase hypertension or (rarely) interstitial nephritis.

-ESR/CRP : if raised this implies infection or an underlying systemic disorder such as vasculitis; an ESR > 100 suggests myeloma. (also suggested by the presence of rouleaux and clumping on the blood film and Bence Jones proteins in urine biochemistry )

The following tests should also be carried out:   

-Electrolytes and renal function: these should be monitored on at least a daily basis; ( watch out for hyperkalemia [more info]  or acidosis )  

-FBC and film (haemolytic uraemic syndrome -recognized by the presence of profound anaemia and thrombocytopenia, together with a blood film showing gross morphological abnormality of the red blood cells [schistocytes] or thrombotic thrombocytopenic purpura)                

-Clotting profile (DIC is suggested by anaemia of greater severity than usual [frequently Hb < 8 g/dl], profound thrombocytopenia, and derangement of clotting tests [prolonged prothrombin, partial thromboplastin and thrombin times; increased levels of fibrin degradation products and D-dimers].

-Calcium and phosphate: Many patients with acute renal failure have hypocalcaemia and hyperphosphataemia, probably secondary to disordered vitamin D metabolism and failure of phosphate excretion, respectively. These abnormalities can develop within a few days. If hypocalcaemia (say, corrected total calcium <2.0 mmol/l) and hyperphosphataemia (say, phosphate >2.5 mmol/l) are profound, then the diagnosis of rhabdomyolysis should always be considered, the urine checked for the presence of myoglobin.

-Cultures: blood, wound swab, urine, sputum( if any).

-Chest x-ray: to identify pulmonary oedema or postoperative pneumonia.  

-ECG: look for features of hyperkalemia (image). Any evidence of perioperative infarct?

-Urinary tract ultrasonography: A scan is necessary to exclude urinary tract obstruction, and small kidneys would signify pre-existing chronic renal disease.

When the cause of acute renal failure is still uncertain, consider:

-serum immunoglobulins (IgA nephropathy)

-electrophoresis (myeloma)

-complement levels (C3/C4 to exclude SLE, infective endocarditis,cryoglobulinaemia)

-ANA[ antinuclear antibodies] and dsDNA( SLE)

-Anti-glomerular basement membrane antibodies (goodpasture’s disease)

-ANCA [Anti-neutrophil cytoplasmic antibodies ](Wegener’s granulomatosus or microscopic polyangiitis)

-ASOT [ Antistreptolysin-O- titre] (post-streptococcal glomerulonephritis)

After the history, examination and investigation, you should be able to narrow down  on the cause of the renal failure (pre-renal, intrinsic renal, post renal). Addressing the cause, after dealing with life threatening complications, is the approach to management.

Management

Underlying principles are:

1. Treat the precipitating cause.

2. Treat life threatening hyperkalemia.

3.Treat pulmonary oedema, pericarditis, and tamponade.

4. Treat volume depletion if necessary.

5. Treat sepsis.

Do the following:

-Catheterize to assess hourly urine output, and establish fluid charts

-Investigations

-Identify and treat hyperkalemia ( Use a cardiac monitor)

-Assess intravascular volume (BP, JVP, skin tugor, fluid balance sheet, weight, CVP  (consider inserting a central venous cannula) 

-If dehydrated, fluid challenge: 250-500mL of colloid or saline over 30 minutes (more info) 

-Reassess; Repeat  challenge if still fluid depleted. Aim for a CVP of 5 to 10cm Water

- Once fluid replete, continue fluids at 20mL+ previous hour’s urine output per hour

-if remains oliguric consider frusemide ( more info) or ‘renal dose’ dopamine (2-5 micrograms/kg/min IV infusion)-(more info)

-Correct acidosis with sodium bicarbonate e.g 50mL of 8.4% IV ( a point of controversy)

-If clinical suspicion of sepsis, take cultures, then treat vigorously. Do not leave possible sources of sepsis (e.g. IV lines) in situ if not needed

- Avoid nephrotoxic drugs, eg NSAIDs, ACE-inhibitors, care with gentamicin (In an endeavour to prevent renal side-effects, and also because of the risk of ototoxicity, aminoglycosides should never be prescribed without the precaution of monitoring the serum concentrations (for gentamicin a typical recommendation would be to aim for a peak concentration of 5 to 10 mg/ml 60 min after intravenous injection, and a trough value of less than 2.5 mg/ml before the next dose).

-Avoid drugs that promote hyperkalemia eg trimethoprim and pentamidine. These antimicrobial agents may contribute to the hyperkalemia often seen in patients infected with HIV who are being treated for Pneumocystis carinii pneumonia.

Hyperkalemia

The danger is ventricular fibrillation. A potassium  >6.5mmol/L will usually require urgent treatment as will those with ECG changes:

-Tall ‘tented’ waves +/- flat P waves +/- increased P-R interval

-Widdening of the QRS complex- leading eventually, and dangerously, to sinusoidal pattern and VF

 

Treatment   

-10mL calcium gluconate (10%) IV over 2 minutes, repeated as necessary if severe ECG changes. This provides cardio-protection. It does not change serum potassium levels. From a clinical viewpoint, it is important to recognize that the effect of calcium infusion is relatively transient. If the plasma potassium concentration is not reduced by other means, then any electrocardiographic improvement that has been obtained is likely to be lost over a period of 20 to 60 min.  

-Insulin + glucose. The plasma potassium concentration can be reduced by 1 to 2 mmol/l over 30 to 60 min by giving an intravenous infusion of glucose and insulin (50 ml of 50 per cent glucose with 10 units of rapidly acting insulin over 15 min).

-Salbutamol: Stimulation of β2-adrenergic receptors leads to activation of the Na–K-ATPase pump and the movement of potassium into cells. This property has been exploited to treat hyperkalaemia in patients with renal failure. Both intravenous salbutamol (0.5 mg over 15 min) and nebulized salbutamol (10 or 20 mg) can reduce plasma potassium concentration by a mean of about 1 mmol/l over 30 to 60 min  

It must be emphasized that none of the treatments described above removes potassium from the body. They may be sufficient as treatment for hyperkalaemia on their own if rapid recovery of renal function can be anticipated, for example following resuscitation of those with prerenal failure or relief of urinary obstruction. However, if rapid recovery cannot be expected, then hyperkalaemia will recur over a period of 2 to 4 hrs as potassium leaks back out of cells, with further doses of calcium, glucose, and insulin tending to have diminished efficacy. Here the period of temporary respite from dangerous hyperkalaemic cardiotoxicity must be used to instigate treatment that will remove potassium from the body.

-Polystrene sulfonate resin (eg. Calcium Resonium, 15g/8h in water) orally or as a 30g  enema (follow up colonic irrigation, after 9h, to remove potassium from the colon).

-Dialysis: Urgent replacement therapy is required if the patient has-

i. Hyperkalemia greater than 6.5 mmol/l or 6-6.5 with ECG changes

ii. Pulmonary oedema unresponsive to medical management

iii. Metabolic acidosis causing circulatory compromise

iv. Uraemic encephalopathy, pericarditis or bleeding.

Modern practice is to initiate renal replacement therapy sooner rather than later (whenever possible), for example when the plasma urea concentration reaches 25 to 30 mmol/l and the plasma creatinine concentration 500 to 700 µmol/l, perhaps even earlier, unless there is clear evidence that renal function is about to recover. There are, however, no controlled trials relevant to modern practice that can be used to justify the initiation of renal replacement therapy at one specific plasma urea or creatinine concentration rather than another.   

Pulmonary Oedema

The immediate management is to sit the patient up, which redistributes fluid from the pulmonary to systemic circulations, and give oxygen by face mask in as high a concentration as possible. Frusemide, or other diuretic agents, are of little benefit in producing diuresis in cases of pulmonary oedema associated with acute renal failure, although they have some vasodilator action that can be beneficial. Intravenous morphine in small doses (2.5 mg, repeated depending upon the response) is very helpful as both a vasodilator and an anxiolytic. Definitive treatment requires the removal of excess fluid—pulmonary oedema being one of the indications for emergency haemodialysis or haemofiltration . In extremis, fluid can be removed by venesection, ideally with the blood returned to the patient later when their pulmonary oedema has resolved and they are comfortably established on haemodialysis or haemofiltration.

Fluid requirements in established renal failure

As a working rule, fluid intake in those with acute renal failure should be limited to the volume of the previous day’s urine output, plus the volume of other measurable fluid losses, plus 500 ml for insensible losses (an allocation that may need to be substantially increased in the presence of fever or in hot environments). However,  fluid-balance charts are frequently inaccurate: thus unthinking adherence to the ‘output plus 500 ml’ rule can lead to problems. There is no substitute for careful, twice-daily clinical examination for signs of intravascular volume depletion or excess, supplemented by accurate daily weighing to gauge overall net fluid balance, with an intelligent, flexible response to the findings.

Nutrition

Feeding should be by the enteral route whenever possible. If the gut is not working and parenteral feeding is required, the regimen used should not be unduly complex to make and to administer, and should not be unnecessarily costly.  Example of feeding regime (not for our Zambian setting, but could be helpful when improvising)

Discussion

It would be important to highlight the different causes of acute renal failure and aids to recognition, just before concluding. Prerenal failure and acute tubular necrosis almost invariably occur in the context of circulatory disturbance—in common parlance, in patients who are shocked. If the patient is not, or has not recently been, in such a state, then it is not likely that their acute renal failure is attributable to either of these conditions and it becomes particularly important to exclude obstructive or intrinsic renal causes. If the circulation is, or has been, deranged, then prerenal failure or acute tubular necrosis is likely.

The differences between pre-renal failure and acute tubular necrosis are purely academic (click). You should know about them because you will be asked in your exams, but in practice the distinction is made retrospectively: patients have pre-renal failure if they start to pass good volumes of urine after volume expansion; if they don’t then they have acute tubular necrosis.

Summary

Many patients with acute renal failure are extremely ill, and the first priority in management is to treat any problems—be they renal or otherwise—that are life threatening. Renal physicians must remember not to concentrate on the kidney to the exclusion of all else: if the patient is not breathing properly, then the first priority is to remedy this, if necessary by intubation and ventilation. The two complications of renal failure that come into the life-threatening category are hyperkalaemia and pulmonary oedema, the specific management of which we have discussed. The next priority is the prompt diagnosis and treatment of hypovolaemia. Finally, the specific diagnosis and treatment of the underlying condition should be addressed: if this persists untreated then renal function will not improve.

Conclusion

I don’t blame you if you have forgotten about our 69 yr old patient. Well a diagnosis of acute renal failure secondary to rhabdmyolosis was made. She was given a fluid challenge and her urine output improved ( as much as 3000mls in 24hrs!). She was maintained strictly on her previous days output with no insensible loss added. The diclofenac was stopped and she was discharged home with review  and monitoring of her renal function by her GP and to be seen after six weeks in fracture clinic.

References

1.Davison, Grunfeld, Cameron, Stewart (1997) -Acute renal disease. Oxford textbook of nephrology. 

2. John D. Firth, Patrick H. Maxwell,  Nick C. Fluck, Philip Kalra, Chris A. O’ Callaghan (2001)-Nephrology. Medical Masterclass Royal College of Physicians.

3. Murray Longmore, Ian wilkinson, Estee’ Torok (2001)- Management of acute renal failure. Oxford handbook of clinical medicine.                 

4. Andy Stein, Janet Wild, Paul Cook (2004)-Acute renal failure. Vital nephrology.

5. HARRISON'S ONLINE Part 11. Disorders of the Kidney and Urinary Tract, Chapter 260. Acute Renal Failure.