Kidney

Kidney  

The main functions of the kidney are to: 

  • Filter rubbish and metabolites out of the body for excretion 

  • Regulation of water and metabolites  

  • Retention of substances like proteins and glucose which may be too big to filter through kidney or have transport mechanisms 

  • Excretion of waste – water soluble and drug products 

  • Acid and base balance – if kidneys go wrong it can cause systemic effects 

  • Endocrine function – production of renin,  aldosterone, ADH, erythropoietin and vitamin D. 

The renin-angiotensin system is responsible for the regulation of blood pressure and fluid/electrolyte balance and controls systemic vascular resistance. 

Structure of the kidney -  

 

Everyone can function with just one kidney.  

Acute Kidney Injury  

  • An abrupt decrease in kidney function that includes but is not limited to acute renal failure.  

Symptoms -  

  • Nausea and Vomiting – due to toxic metabolites building up in kidney 

  • Peripheral Oedema – a build up of water in tissues  

  • Breathlessness – due to oedema  

  • Pulmonary oedema - fluid in lungs so cannot exchange gases properly 

  • Itching – toxic metabolites under skin 

  • Pleural Effusion - fluid around lungs 

  • Weakness – the kidney cannot excrete toxins so there is an homeostatic imbalance 

  • Pericarditis – inflammation around the heart 

  • Decreased consiousness  

  • Oliguria – low urine output 

  • Convulsion – metabolite and water imbalance 

AKI – there are 3 main causes  

  1. Pre-renal – caused by the inadequate perfusion of otherwise normal kidneys e.g peripheral vasodilation in sepsis (sepsis is the most common cause of pre-renal. Hypotension (low blood pressure)/ Hypovaleamia (decreased blood volume e.g due to nausea, vomiting, diarrhoea if fluid is not replaced). Unusual in ‘normal’ kidneys as able to regulate perfusion well. 

  1. Renal – damage to kidney and the surrounding vasculature e.g blockage/inflammation of the blood vessels and drugs such as NSAIDs  

  • NSAIDs can cause kidney damage because they inhibit prostaglandins which are responsible for vasodilation in the kidneys, therefore if a patient takes NSAIDs they can cause constriction which can cause blockage of renal blood vessels. 

  1. Post Renal – obstruction of urinary outflow e.g kidney stones or serious trauma/ tissue/muscle damage causing increased levels of creatinine (product of broken muscles) which blocks kidneys. 

AKI outcomes and goals of treatment =  

  • Significant mortality and morbidity  

  • An AKI can cause chronic kidney damage  

  • GOALS of treatment = prevent further damage and facilitate recovery of renal function. Treatment of AKI mainly involves removing the underlying cuase and giving the patient fluids.  

  • 20% of AKU cases are predictable and avoidable!  

 

AKI classification and alerts  

  • The 2 main measures of kidney function are creatinine and urine output.  

  • Anuria = no urine output  

 

 

Chronic Kidney Disease (CKD)  

  • CKD is defined as a reduction in renal function or structural damage within the kidneys or both. It lasts over a period of 3 months and is associated with health implications. Therefore, you should keep an eye on Acute Kidney Injury patients as it may develop into chronic kidney disease 

AKI vs CKD 

  • Cannot rely on blood results alone as AKI and CKD both present with similar blood profiles – however may be useful to look at previous blood results as they may give a better picture as you can look particularly at the serum creatinine levels and observe patterns in the results  

  • CKD presents in patients that have a history of being vaguely unwells e.g anaemia, long-standing hypertension, neuropathy, dizziness, breathlessness, lethargy etc.  

  • If the patient has a renal ultrasound, the kidneys are usually normal in AKI but in CKD there is likely to be structural and perfusion damage.  

  • Bone disease can be present in AKI or CKD due to hyperphosphataemia and hypocalcaemia, elevated parathyroid hormones and radiological evidence of bone disease e.g osteoporosisis and more common fractures.  

CKD Classifications  

  • EGFR is the glomerular filtration rate and is a measure of creatinine clearance 

- Haematuria (blood in urine), proteinuria (high levels of protein in urine) or microalbuminuria (high levels of albumin in urine) can be identified with a urine dipstick test. 

 

When should you refer a patient with CKD for a specialist review? 

  • GFR less than 30ml/min/1.73m2 

  • Suspected renal artery stenosis – the narrowing of one or both renal arteries  

  • Suspected Genetic conditions  

  • GFR declining by more than 15ml/min in 12 months  

  • Alb:creat more than 30mg/mmol with haematuria (blood in urine) 

  • Alb:creat more than 70mg/mmol without diabetes 

  • Uncontrolled hypertension despite 4 drugs  

 

The secondary care treatment goals for CKD are to manage and delay the progression of CKD, optimise care and prevent secondary complications and have long term plans when the eGFR is less than 15ml/min/1.7m2 e.g dialysis, transplantation and conservative/end of life care.  

 

Long term consequences of CKD =  

  • Hypertension can be a cause or consequence of CKD because there is a lack of homeostasis which means patients cannot control blood pressure 

  • Anaemia – iron/vitamin deficiency due to a decreased production of erythropeietin (erythropoietin is a hormone that helps the body produce red blood cells) 

  • Renal Bone disease because the calcium and phosphate homeostasis is disturbed – there is an increase in serum phosphate due to a decrease in phosphate filtration which causes a decrease in serum calcium levels due to phosphate problems and decreased vitamin D synthesis which then causes an increase in the parathyroid hormone (hyperparathyroidism) resulting in calcium release from bones leading to long term bone disease.  

  • Cardiovascular disease  

  • Oedema – due to sodium and water retention which can build up on the lungs causing breathlessness.  

  • Pruritis (itching) due to uraemia which means there is excess urea in the blood which can get under the skin and cause itchiness.  

  • Restless leg syndrome due to electrolyte imbalances that impact sleep and are only relieved by moving  

  • Nausea due to accumulation of urea and other toxins  

  • GI ulceration 

Management of CKD  

  • Treat underlying cause  

  • Diet  

  • Renoprotection – control hypertension and decrease proteinuria  

  • Control of Cardiovascular risk factors e.g give patients medications such as statins  

  • Correction of anaemia  

  • Management of calcium, phosphate and potassium levels – patient may require vit D/calcium supplements to keep levels balances  

  • Suppression of PTH  

  • Dialysis  

  • Transplant  

Renal Prescribing Principles – drug handling  

  • Absorption – unpredictable absorption of drugs in uraemia so may need to alter dosing for effectiveness 

  • Distribution – decreased protein binding affected by fluid overload or depletion. Fluid overload or depletion can alter how drugs bind to proteins, affecting their distribution in the body 

  • Metabolism – decreased catabolism (e.g insulin) and decreased conversion of precursors to active metabolites e.g vitamin D 

  • Excretion- The elimination of drugs that are excreted by the kidneys is reduced, leading to potential toxicity. 

  • Pharmacodynamic alterations – uraemia, NSAIDs and diuretics less affective 

Choice of drug -  

  • Not nephrotoxic (toxic to kidneys) 

  • Large therapeutic index  

  • Does not require renal metabolism  

  • Does not require renal excretion  

  • Low adverse effect profile  

  • Not highly protein bound  

  • Reach site of action in high enough concentrations for therapeutic effect 

  • When choosing a drug you may have to decrease the drug dose and increase dosing intervals for example 

  • If giving by IV, Its also important to look at sodium levels and use an alternative such as glucose if you can or choose low sodium at the smallest possible volume.  

 

Drug factors -  

  • How essential is it? 

  • Is there a better alternative  

  • Is there a parameter that can be monitored for efficacy and safety? 

  • Is the drug more likely to cause side effects?