Treatment And Pathogenesis Of Acute Hyperkalemia Pdf
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Hyperkalemia HK is the most common electrolyte disturbance observed in patients with kidney disease, particularly in those in whom diabetes and heart failure are present or are on treatment with renin—angiotensin—aldosterone system inhibitors RAASIs.
- Treatment and pathogenesis of acute hyperkalemia
- Hyperkalaemia in Adults
- Third in a series on hyperkalemia: current views on the treatment of hyperkalemia
Metrics details. As the field of Primary Aldosteronism PA becomes ever expanded, diagnosis of PA is increasingly diagnosed by endocrinologists. With increased PA screening, many of the cases are now found in patients with complex co-morbidities in addition to their hypertension. Serum aldosterone was high with low renin activity leading to high aldosterone to renin ratio ARR.
Treatment and pathogenesis of acute hyperkalemia
Hyperkalemia HK is the most common electrolyte disturbance observed in patients with kidney disease, particularly in those in whom diabetes and heart failure are present or are on treatment with renin—angiotensin—aldosterone system inhibitors RAASIs. HK is recognised as a major risk of potentially life threatening cardiac arrhythmic complications. When an acute reduction of renal function manifests, both in patients with chronic kidney disease CKD and in those with previously normal renal function, HK is the main indication for the execution of urgent medical treatment and the recourse to extracorporeal replacement therapies.
In patients with end-stage renal disease, the presence of HK not responsive to medical therapy is an indication at the beginning of chronic renal replacement therapy. HK can also be associated indirectly with the progression of CKD, because the finding of high potassium values leads to withdrawal of treatment with RAASIs, which constitute the first choice nephro-protective treatment.
It is therefore essential to identify patients at risk of developing HK, and to implement therapeutic interventions aimed at preventing and treating this dangerous complication of kidney disease. Current strategies aimed at the prevention and treatment of HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials where optimal treatment and monitoring are mandatory.
This position paper will review the main therapeutic interventions to be implemented for the prevention, detection and treatment of HK in patients with CKD on conservative care, in those on dialysis, in patients in whom renal disease is associated with diabetes, heart failure, resistant hypertension and who are on treatment with RAASIs, and finally in those presenting with severe acute HK.
HK, besides being associated with fatigue and muscle weakness, remarkably increases the risk of sudden death due to fatal arrhythmias [ 4 ], and acts as major driver to start chronic dialysis therapy in patients with end-stage renal disease ESRD [ 5 ].
The clinical relevance of HK has recently been confirmed by a meta-analysis of 27 cohort studies, 10 in the general population, seven in individuals at high cardiovascular risk, 10 in CKD patients, including a total of 1,, subjects followed for an average of 6. Despite the epidemiologic dimensions of HK and its negative effects on CKD outcome, current therapeutic strategies are far from optimal. A recent observational study from Italy has confirmed the limits of current approaches to HK even in the setting of renal clinics, i.
This historical prospective study examined outcomes and determinants in as many as CKD patients referred to 46 Italian outpatient nephrology clinics.
In either visit, mean sK was similar 4. Over a median follow up of 3. In contrast to an unselected CKD population, mortality did not increase in these patients under stable nephrology care.
This finding is expected if one considers the attitude of nephrologists starting dialysis in stage 5 when HK, even when of moderate degree, becomes refractory to medical therapy in order to prevent additional increments of sK potentially associated with fatal arrhythmias [ 5 ]. An additional but important grey area in the management of HK is the treatment of this electrolyte abnormality in dialysis patients. HK is more common during the long interdialytic interval and in patients treated with RAASIs to treat underlying cardiovascular disease as in those that need hypertonic dialysate because of poor intradialytic hemodynamic stability [ 12 , 13 ].
In dialysis patients, the higher the sK values the worse is the prognosis hospitalization, admission to emergency department and death [ 14 , 15 ]. Finally, the optimal management of acute severe HK, which is a true nephrology emergency that requires prompt and efficacious intervention, still remains to be clarified [ 16 ].
For the aforementioned reasons, the Italian Society of Nephrology has recently established a working group to develop practical recommendations on the clinical management of HK, in terms of monitoring and treatment.
This position statement is the final output of the collaborative work and it is divided into four sections that address the main aspects of HK in CKD population:. In-depth evaluation of the CKD patients with high sK is the key for graduating intensity of K-lowering treatment. The first objective is to correctly identify patients at high risk of developing more severe and potentially life threatening episodes of HK. Proper assessment is based not only on the exclusion of pseudohyperkalemia spurious increases of sK usually due to hemolysis of blood samples caused by fist clenching or prolonged use of tourniquet during phlebotomy or delay in processing blood samples , but also on the decision of the correct timing of testing sK.
Guidelines suggest measuring sK prior to first prescription or uptitration of RAASIs and in the first two subsequent weeks [ 17 , 18 ].
In the presence of elevated or increasing levels of sK, exclude pseudohyperkalemia, extend evaluation to all potential co-determinants of HK and anticipate control visit.
This definition must therefore take into account the effect of sK on the global prognosis of the CKD patient. Therefore, even minimal sK abnormalities should call for attention, because they herald more important changes potentially associated with fatal arrhythmias. These recommendations aimed for the general population may not hold true in CKD patients, due to the intrinsically higher risk of HK. This aspect is particularly important in CKD, where fecal loss of K increases with a decline in GFR, as a major compensatory mechanism [ 24 , 25 ].
While waiting for more and solid evidence on K intake and outcome in mild-to-moderate CKD, it appears useful to maintain a nutritional approach, that is prudent but not restrictive in K intake a priori. On the contrary, patients with advanced CKD should be considered as those under chronic dialysis therapy, that is, they should restrict their daily dietary intake of K see following paragraph and position statement 2.
At variance with patients with advanced CKD, in non-dialysis CKD of mild-to-moderate degree, restriction of K intake is not recommended unless sK levels are above 5. Treatment of mild-to-moderate chronic HK sK 5. However, bicarbonate appears less effective in reducing sK in patients with advanced CKD [ 25 ].
However, this measure is indicated exclusively in the presence of extracellular volume expansion. Furthermore, these two binders must be withdrawn when sK levels drop below 5. This therapy therefore is not suitable to enable chronic cardio-nephroprotective therapy with RAASIs, and indeed the two mentioned binders are de facto poorly used in the real world [ 3 ].
Two new potassium-binding drugs, namely patiromer and sodium-zyrconium cyclosilicate, not yet available in our country, have undergone extensive clinical testing recently in the setting of chronic hyperkalemia where they have been shown to be effective and relatively safe during long-term administration.
However, HK is quite frequent in the dialysis setting, more in hemodialysis HD than in peritoneal dialysis PD because of the continuous nature of the latter. Differences in reported rates of HK observed between clinical trials are mainly related to heterogeneity in HK definition and patient population, as well as the number of sK tests performed.
Peritoneal fluids are potassium-free, and K balance is maintained by the continuous nature of the treatment, preserved residual kidney excretion, increased colonic secretion of K, decreased intake of K-rich foods, and transcellular shift driven by insulin release in response to the obligatory glucose absorption from the PD fluids. HK is the most important electrolyte abnormality in dialysis because it can cause cardiac arrhythmias. Nephrologists try to avoid rapid intradialytic changes of sK by using different models of K removal to limit K gradient between serum and dialysate [ 30 ].
However, there is no solid evidence that these approaches improve survival [ 31 ]. The lower mortality rates were observed in hemodialysis with pre-dialysis sK values ranging 4. Serum K should be kept in the range 4. Although K is directly removed from plasma, the distribution of K between the plasma and interstitial fluid is nearly instantaneous; therefore, it is immediately removed from the extracellular fluid. Since replenishment from cellular stores continues when K removal stops, there is a substantial post-dialysis rebound of sK, ranging from 0.
Several factors influence dialysis K removal, namely dialysis modality, treatment time, frequency of sessions, residual diuresis, dietary intake, gastrointestinal loss, glycaemia and insulin fluctuations, metabolic acidosis, as well as the use of many drugs, mainly RAASIs [ 13 ]. The lower the dialysate K concentration, the greater the amount removed, and the lower the final post-dialysis sK. However, the use of low K dialysate may expose patients to potential cardiac side effects.
Given that the kidneys are the major route for excretion of dietary K, limiting K intake is critical in functionally anephric dialysis patients. Because HK is currently and frequently recognized in the dialysis setting, it is quite clear that current strategies do not allow the full control of HK [ 9 ].
Inadequate dialysis, due to erroneous prescription, poor patient compliance or vascular access insufficiency, are additional common risk factors for HK. Therefore, in HK patients it is essential to evaluate dialysis efficiency modality, dose, treatment time, session frequency, blood and dialysate flow, dialysate K concentration etc.
Different schedules often need to be considered such as prolonged dialysis time, alternate-day or daily dialysis [ 38 ], or profiled hemodialysis K removal [ 30 ]. The latter may be useful in order to avoid high and potentially harmful K gradient between serum and dialysate and post-dialysis K rebound, that are both related to arrhythmias and cardiac arrest [ 15 ].
Therefore, we need an adequate mass balance while avoiding excessive changes in serum concentrations. Finally, an additional obstacle to consider in the chronic management of HK in patients on dialysis is the infrequent monitoring of serum K levels, which are generally measured monthly. When HK is repeatedly detected, dialysis prescription must be re-evaluated: dose, blood and dialysate flow, treatment time and frequency in hemodialysis schedule.
In dialysis patients, dialysis schedule, dietary intake and concomitant drugs need to be revised. If HK control is still inadequate, K binders need to be considered. SPS, which exchanges sodium for calcium, ammonium, and magnesium in addition to K, is available since It is most effective in binding K when it reaches the rectum, either by enema or by oral administration with cathartics. Moreover, when using SPS in dialysis the risk of volume overload needs to be taken into account.
DM is indeed associated with increased risk of chronic HK, due to blunted insulinemic response to hyperglycemia with reduced K switch to intracellular fluid, plasma hyperosmolality, with enhanced K switch to extracellular fluid, and hyporeninemic hypoaldosteronism, with impairment in K tubular secretion, which plays a major role, especially in type 2 DM.
Also in DKD, the prevalence of chronic HK progressively increases along with increasing number of samplings [ 46 ]. This is a matter of concern since chronic therapy with RAASIs is strongly recommended by currently available international guidelines for the management of albuminuric DKD at high risk of progression to ESRD [ 17 ], since albuminuria reduction was shown to be associated with a significant reduction in the risk of subsequent ESRD [ 47 ].
In fact, HK is associated with increased mortality in the diabetic population and highest rates were observed when CKD coexists [ 44 ]. Therefore, in clinical practice, ensuing HK is frequently associated with downtitration or even withdrawal of RAASIs therapy [ 46 ], even though this strategy seems to be associated with unfavorable clinical outcome.
It appears that downtitration or even withdrawal of RAASIs for safety reasons although controlling or even preventing chronic HK misses the opportunity of offering DKD patients the best available renoprotective therapy. Full or maximum tolerable dose of RAASIs medication should be offered to patients with DKD, especially in those with reduced eGFR, in order to maximize nephro- and cardioprotective effects of these drugs.
Recently, new available agents, such as patiromer and sodium-zirconium cyclosilicate have shown to be effective in controlling HK in DKD patients, with good dose—response and safety profiles [ 55 , 56 ]. In order to offset chronic HK in patients on full or maximum-tolerable dose of RAASIs, it is important to adopt an adequate treatment and nutritional approach to reduce HK. This suggests that all therapeutic strategies aimed at lowering sK should be adopted in an effort to improve in the management of this chronic electrolyte disorder mostly in high-risk patients, such as those with DKD, who may benefit from optimal treatment with RAASIs, as recommended by available international guidelines.
These data underscore the importance of optimally treating CKD patients with HF to reduce the high incidence of mortality. The problem of the occurrence of HK is a crucial point for the treatment of HF in patients, both in the absence and in the presence of CKD. Patients taking submaximum doses or who discontinued ACEIs had worse outcomes than patients taking maximum doses of the drug.
Similar outcomes were observed between those who were undertreated and those who discontinued the drug [ 54 ]. If these data were confirmed, the number of HF patients with dangerous values of sK would increase by many units, particularly in the subgroup of subjects with HF and CKD. An article published a few years later showed that publication of the RALES study was associated with an increase in the rate of spironolactone prescriptions and in hyperkalemia-associated morbidity and mortality [ 66 ].
However, the risk of HK and renal failure was higher in those with worse baseline renal function, particularly in the spironolactone arm [ 67 ]. MRAs therapy was associated with lower risk of long-term all-cause readmission, but greater risk of readmission for HK and acute renal failure [ 70 ]. The authors evaluated the association between baseline renal function and the efficacy and safety of the drug over a 4-year follow-up period.
However, it is also evident that this population is more at risk for the occurence of HK, a potentially very dangerous complication in terms of hospitalization and mortality. Providing nephrologists with the necessary tools to enable them to control the onset of HK should significantly improve the prognosis of CKD patients with HF. The drugs that the cardiology guidelines recommend for the treatment of patients with HF are effective in reducing adverse events, re-hospitalizations and mortality, even in patients with the simultaneous presence of HF and CKD.
Therefore, there should be no difference in the therapeutic approach in patients with HF with and without CKD. All of these classes of drugs can lead to hyperkalemia, particularly in patients with reduced GFR and those experiencing a worsening of renal function. In these patients, all dietary and pharmacological measures should be implemented to prevent and control increases in sK, before reducing or discontinuing ongoing therapies.
In HF patients with CKD who are not taking RAASIs therapy because of high sK values, all dietary and pharmacological measures should be implemented to reduce sK and allow them to receive appropriate treatment for their cardiological disease. Resistant hypertension is associated with a poor prognosis. Amiloride significantly reduced SBP, not different from spironolactone [ 73 ]. The results suggest that RH is commonly a salt-retaining state, most likely due to inappropriate aldosterone secretion.
In accordance with these findings, in recent years, an increasing body of evidence has shown benefit of MRAs, such as eplerenone and spironolactone, in improving BP control in patients with RH. The antihypertensive effects were assessed in patients included in four trials.
Hyperkalaemia in Adults
Lauren A. Kimmons, Justin B. Secondary hyperkalemic paralysis is an uncommon but potentially life-threatening consequence of drug-induced disease. We report a case of a year-old female with history of chronic kidney disease presenting to the emergency department with a one-day history of upper and lower extremity weakness and paresthesias. Electrocardiogram showed first-degree atrioventricular block with peaked T waves. Symptoms and electrocardiogram returned to baseline within 24 hours of presentation and serum potassium returned to 4. This case emphasizes the importance of including such a condition in the differential diagnosis of patients with ascending paralysis and the importance of close monitoring of patients placed on potassium-elevating agents.
Third in a series on hyperkalemia: current views on the treatment of hyperkalemia
Hyperkalemia has remained a challenging and important issue for more than three decades with the emergence of highly advanced critical care medicine. Critical Care Units CCU are equipped with electrolyte analyzers, which enable quick diagnosis of electrolyte status, and electrocardiogram ECG and cardiac monitors to recognize ECG changes that occur with hyperkalemia, helping to detect life-threatening arrhythmias. Hyperkalemia has always demanded extremely prompt intervention through different pharmacotherapeutic measures. Further objectives involve the prevention of hyperkalemia recurrence with novel drugs for chronic use. Two novel oral therapies are in development for both acute and extended use in the management of hyperkalemia, sodium zirconium cyclosilicate and patiromer sorbitex calcium [1,2].
Hyperkalemia is a frequent finding in patients with chronic kidney disease CKD. This increase in serum potassium levels is associated with decreased renal ion excretion, as well as the use of medications to reduce the progression of CKD or to control associated diseases such as diabetes mellitus and heart failure. Hyperkalemia increases the risk of cardiac arrhythmia episodes and sudden death.
Common causes of hyperkalemia include kidney failure , hypoaldosteronism , and rhabdomyolysis. Initial treatment in those with ECG changes is salts, such as calcium gluconate or calcium chloride.