Irish Medical News


Complications of chronic kidney disease


Chronic kidney disease (CKD) includes any conditions that affect the kidney with the potential to cause either progressive loss of kidney function or complications resulting from decreased kidney function. Increasing evidence indicates that the adverse outcomes of CKD, such as kidney failure, cardiovascular disease, and premature death, can be prevented or delayed.


Earlier stages of CKD can be detected through laboratory testing, and treatment of earlier stages of the disease is effective in slowing the progression toward kidney failure. Initiation of treatment for cardiovascular risk factors at earlier stages of CKD should be effective in reducing cardiovascular disease events both before and after the onset of kidney failure.

Unfortunately, CKD is underdiagnosed and undertreated, resulting in lost opportunities for prevention. We need to develop a “renal radar”– a better lookout system for detecting and hopefully preventing kidney disease. Most patients with mild to moderate CKD will never require dialysis and should be managed in primary care.

Kidney disease is strongly associated with marked increase risk of cardiovascular death – 50 per cent of heart failure patients have kidney failure and vice versa. Estimated glomerular filtration rate (eGFR), which measures renal function, is a risk factor for cardiovascular disease just like hypertension, cholesterol level and diabetic status. Appropriate management of patients reduces overall cardiovascular risk and delays progression to renal failure.

In its early stages, chronic kidney disease is characterised by kidney damage and level of kidney function. CKD in later stages is defined as an estimated eGFR, for at least three months, of <60 mL/min/1.7m2. Stages of kidney disease are ranked by classifying severity of disease with declining eGFR and kidney damage. Amongst healthy young adults, average GFR vales are 127ml in men and 118 ml in women – GFR on average decreases by about 1ml/min/1.73m2 per annum from 30 years of age. Many healthy but elderly patients will have a GFR level of <60.

As an index of kidney function, GFR has numerous advantages: It makes it easier to notice declining renal function; its level correlates with severity of complications and the severity of kidney damage; and the level is reduced before signs and symptoms of uraemia appear.

Once the diagnosis of CKD is established, the etiology of the disease needs to be elucidated. Often the etiology can be determined by history alone; however, reversible causes of CKD should be considered in all patients. Regardless of the underlying etiology of the CKD, a GP can make its progression through strict blood pressure control, tight glycaemic control, reduction in the degree of proteinuria, and smoking cessation.

All CKD patients are at significantly increased risk of cardiovascular events; therefore, additional cardiovascular risk factors such as hyperlipidaemia should be managed aggressively. Assessment for the complications of CKD, including anaemia, bone metabolism abnormalities, metabolic acidosis, and malnourishment should be assessed once the GFR declines below 60mL/min/1.73m2 (stage 3). Early screening and treatment of these complications can prevent the development of further sequelae and should not be delayed until referral to nephrology.

In a retrospective study of over 1,000 patients with chronic renal failure, 69 per cent died during follow up (5.5 years) and 46 per cent of deaths were cardiovascular. Patients were 15 times more likely to die than to require dialysis.

The main factors in the progression of renal failure include genetic determinants, age of onset of nephropathy, sex and underlying disease.
Modifiable factors include blood pressure control and the degree of urinary protein excretion.

Although multiple organs are affected and many different specialties express interest in its management, hypertension is basically a kidney disease. If we control hypertension, we control the kidney.

Cardiovascular protection in high-risk groups is vital. Most patients are advised to take at least three or four antihypertensives, antiplatelet agents and lipid-lowering drugs. Blockade of the renin angiotensin system is reno-protective, and achieved blood pressure is the most important determinant of risk.

When renal disease is present, initial therapy should either be an ACE inhibitor or angiotensin II receptor blocker (ARB). Most trials note a 24-50 per cent reduction of overt nephropathy on this treatment, independent of BP reduction.

In the ONTARGET trial the ARB telmisartan was noninferior to the ACE inhibitor ramipril in patients with vascular disease or high-risk diabetes. However, the combination of the two drugs was associated with more adverse events without an increase in benefit.

ACE inhibitors reduce cardiovascular morbidity and mortality in patients with vascular disease or high-risk diabetes. ACE inhibitors do not block the production of all angiotensin II and have the additional action of enhancing bradykinin, which leads to the side effects of cough and angioedaema. The ONTARGET authors therefore conducted their study to test whether an ARB (which blocks the effects of angiotensin II without enhancing bradykinin) was similarly effective to an ACE inhibitor and whether the combination of an ACE inhibitor and an ARB may be superior.

Patients given the combination treatment had higher rates of hypotensive symptoms, syncope, renal dysfunction, and hyperkalaemia, with a trend toward an increased risk of renal function requiring dialysis.
There are now products that combine an ACE inhibitor/ARB with a calcium channel blocker (CCB), and have a good evidence base. It is also easier to get a patient to take just one tablet.

In the ACCOMPLISH trial, superior outcomes were seen with an ACE inhibitor/amlodipine combination versus ACE/hydrochlorothiazide (HCTZ). This trial showed that in patients with hypertension at high-risk for cardiovascular events, combination treatment with benazepril plus amlodipine reduced progression of CKD more effectively than did benazepril plus HCTZ. This benefit was also seen when cardiovascular or all-cause mortality were assessed with progression of CKD. Differences in blood pressure control throughout the study could not account for these findings. 

References on request

Dr George Mellotte, Senior Lecturer in Medicine, Trinity College Dublin and Consultant Nephrologist, St James’s Hospital, Dublin

World Kidney Day took place on March 10. For more information visit


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