Therapeutic Targets
- Prevent progression (progression) of chronic renal failure (nephroprotection/protection of kidneys) [review current medications: see “Renal function-dependent and -independent drugs” list below].
- Normalization of blood pressure; in chronic kidney disease, optimal blood pressure appears to be 130-159/70-89 mmHg.
Therapy recommendations
- The KDIGO (Kidney Disease: Improving Global Outcomes) international therapy guidelines recommend RAAS blockade by.
- ACE inhibitors (nephroprotection; first-line agent) and
- Angiotension II receptor antagonists (nephroprotection) in hypertensive (with high blood pressure) diabetic and nondiabetic adults with chronic kidney disease and albuminuria (appearance of albumin in urine) of >300 mg/d.
- DAPA-CKD (double-blind study: 4,031 patients were treated with either 10 mg/d dapagliflozin or placebo): Therapy with the SGLT2 inhibitor in patients with renal disease reduces the risk of renal failure, protects against heart failure, and prolongs life, regardless of diabetes status (risk significantly reduced by 29%).CONCLUSION: The SGLT2 inhibitors should be included in the standard therapy of CKD patients.
- Regular laboratory checks to determine electrolytes/blood salts (Na, K, Ca, Cl, Mg).
- A fluid intake of 2.5 l/d should be aimed for (urea excretion ↑).
- If necessary, diuretic administration (drug for drainage) to increase diuresis (prophylaxis of overhydration): e.g., furosemide (loop diuretic); in case of loss of effect due to compensatory sodium reabsorption in the distal tubule, additional administration of a thiazide diuretic (inhibition of sodium reabsorption in the distal tubule) [= sequential nephron blockade].
- See also under “Further therapy.”
Note: Patients with chronic renal insufficiency benefit significantly from dapagliflozin. In addition, the following pathologies (pathological conditions) should be treated:
- Hyperglycemia: blood glucose control or glycemic control. Good glycemic control can lead to a reduction in albuminuria and thus delayed progression of chronic kidney disease (CKD) (see below Diabetes mellitus/Drug therapy):HbA1c < 7%In type 2 diabetics and presence of chronic renal insufficiency in CKD stage G3, metformin can reduce the risk of death and cardiovascular events but cannot halt renal function loss.
- Patients with chronic renal failure have an increased incidence of hyperuricemia and gout due to impaired renal elimination of uric acid. This leads to precipitating uric acid crystals, which are phagocytosed (“eaten up”) and activate the multiprotein complex inflammasome in the cell (see below hyperuricemia/medicinal therapy).
- Chronic disorders of the acid-base balance (metabolic acidosis / metabolic acidosis) – sodium bicarbonate.
- Hyperlipidemia (dyslipidemia) – statins are first-line agents; these also reduce the rate of reduction in estimated glomerular filtration rate (eGFR) and slow the progression (progression) of pathologic proteinuria (increased excretion of protein in urine); in end-stage renal failure (dialysis), statins reduce the risk of first-ever onset of atrial fibrillation (see u. respective form of hyperlipidemia (lipid metabolism disorder)/Medicinal therapy)Note: The lower the renal function, the lower the effect of statin therapy.
- Compensation of a metabolic acidosis (HCO3- < 22 mmol/l): e.g., with potassium and magnesium citrate.
- Renal anemia (renal anemia) – iron substitution and erythropoietin (Epo) as the drug of choice (see below renal anemia / drug therapy).
- Secondary hyperparathyroidism (parathyroid hyperfunction)/calcium–phosphate metabolic disorders – calcimimetics, phosphate restriction, vitamin D analogues (see below Hyperparathyroidism/Medicinal Therapy).
- Hyperkalemia (excess potassium) – treatment with cation exchanger (sodium zirconium cyclosilicate).
Active substances (main indication) for the treatment of hyperkalemia (potassium excess).
See under hyperkalemia / drug therapy.
Agents for treatment for the treatment of thrombophilia (tendency to thrombosis).
Anticoagulants because of risk of thrombosis in early renal failure: NOAKs (new oral anticoagulants) are superior to VKAs (vitamin K antagonists) in atrial fibrillation and early renal failure (= patients not requiring dialysis) (systemic embolisms in general (-21 percent), deaths (-12 percent), hemorrhagic insults (-52 percent)).
Renal function-dependent and -independent drugs (modified by)
| Group | Renal function dependent | Renal function independent |
| Analgesics | Acetylsalicylic acid Diclofenac Ibuprofen Indometacin Metamizole Paracetamol Morphine (M6-glucurinide) Pethidine (Norpethidine) Tramadol | Fetanyl levomethadone buprenorphine |
| Antiarrhythmics | Sotalol ajmaline quinidine flecainide lidoain | Amiodarone |
| Antibiotics | Aminoglycosides gyrase inhibitors penicillins carbapenems cephalosporins ciprofloxacin macrolides | Doxycycline moxifloxacin roxithromycin |
| Antidepressants | mirtazapine venlafaxine | |
| Antidiabetic | Gliquidone* Gliclacid* Glibenclamide* Glimepride* (hydroxymetabolite) Sitagliptin Metformin* * Repaglinide Rosiglitazone | Nateglinide* * * pioglitazone saxagliptin* * * * |
| Antiemetics | Granisetron domperidone metoclopramide | Aprepitant |
| Antiepileptic drugs | Clonazepam gabapentin lamotrigine levetiracetam oxcarbazepine pregabalin | Carbamazepine Phenytoin Valproate |
| Antihistamines | Cetirizine Loratardine Cimetidine Famotidine Ranitidine | |
| Antihypertensives | Atenolol sotalol captopril enalapril ramipril irbesartan losartan amlodipine clonidine urapidil | Bisoprolol carvediol metoprotol propranolol |
| Antifungals | Amphotericin fluconazole itraconazole | Caspofungin |
| Antiobstructive agents | Fenoterol salbutamol theophylline | Budesonide |
| Antiparkinsonian | Amantadine biperidene pramipexole | Entacapone |
| Gout remedy | Allopurinol (metabolite oxipurinol) | Colchicine, febuxostat, |
| Cardiovascular drugs | Digoxin molsidomine | Digitoxin |
| Hypnotics | Bromazepam diazepam flunitrazepam oxazepam zopiclone | Zolpidem |
| Immunosuppressants | Azathioprine ciclosporin (cyclosporin A) | Sirolimus (rapamycin) Tacrolimus |
| Lipid-lowering agents | Bezafibrate, fenofibrate | Simvastatin, niazine |
| Migraine medication | Almotriptan Sumatriptan | |
| Neuroleptics | Melperone sulpiride fluphenazine clozapine lithium olanzapine risperidone | |
| Proton pump inhibitors | Omeprazole Lansoprazole Pantoprazole | |
| Psychotropic drugs | Lithium, mirtazapine | Amitriptyline, citalopram, haloperidol, risperidone |
| Antirheumatic drugs | Methotrexate (MTX) | Hydroxychloroquine, leflunomide |
| Thyroid medications | Carbimazole Thiamazole | |
| Secretolytics | Ambroxol bromhexine | |
| Tuberculostatics | Ethambutol isoniazid pyrazinamide streptomycin | Rifampicin |
| Antivirals | Aciclovir foscarnet ganciclovir | Brivudine Lopinavir |
| Urology | Sildenafil Vardenafil Tolterodine | |
| Cytostatics* * * * * | Actinomycin D, bleomycin, capecitabine, carboplatin, cisplatin; cyclophosphamide, doxorubicin, epirubione, etoposide, gemcitabine (dFdU), ifofamide, irinotecan, melphalan, methotrexate, oxaliplatin, topotecan | Anastrozole, docetaxel, doxorubicin PEG liposomal, erlotinib, fluorouracil, gefitinib, leuprorelin, megestrol, paclitaxel, tamoxifen, terozol, vincristine, trastuzumab |
| Other | Iodine-containing radiographic contrast agent interferon |
From CKD(renal insufficiency/kidney weakness) stage 3 (GFR < 60 ml), many drugs must be adapted to renal function. * From CKD stages 4 to 5, sulfonylureas are contraindicated * * Contraindications: Renal failure or renal dysfunction with creatinine clearance < 30 ml/ min, and acute conditions that may lead to impaired renal function * * * Dose adjustment for CKD stages 4 to 5 * * * * Saxagliptin can be used up to CKD stage 5 * * * * * Cytostatic agents must be reduced to 40-80% of the standard dose on average in dialysis patients. This list is not to be considered complete!In the case of renal insufficiency and type 2 diabetes mellitus, please note the half-life (HWZ) of the antidiabetic drugs! (see Diabetes mellitus type 2/Medicinal therapy).
ACE inhibitors
ACE inhibitors are drugs that inhibit the angiotensin-converting enzyme. Angiotensin is a hormone that has a strong vasoconstrictor (narrowing of blood vessels) and antinatriuretic effect – decreasing sodium excretion in the urine – and thus increases blood pressure. ACE inhibitors inhibit the conversion to the effective form. As a result, blood pressure drops. This group includes captopril and ramipril. Enalapril + folic acid helps slow the progression of mild to moderate chronic kidney disease in patients with hypertension compared with enalapril monotherapy alone.
Angiotensin II receptor antagonists*
The so-called sartans compete with angiotensin for receptors and thus lead to a reduction in blood pressure. The mechanism of action is similar to that of ACE inhibitors. Well-known agents from this group are losartan and candesartan. * Angiotensin II antagonists (synonyms: AT-II-RB; ARB; angiotensin II receptor subtype 1 antagonists; angiotensin receptor blockers; AT1 receptor antagonists, AT1 receptor blockers, AT1 antagonists, AT1 blockers; angiotensin receptor blockers, sartans).
Note: The combination of ACE inhibitors and AT-1 antagonists should be avoided!
Supplements (dietary supplements; vital substances)
Appropriate dietary supplements should contain the following vital substances:
- Vitamins (D3* , thiamine* (vitamin B1), pyridoxine* (vitamin B6), folic acid* ).
- Minerals (calcium* )
- Trace elements (iron* , selenium* , zinc* )
- Fatty acids (omega-3 fatty acids* * : Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)).
- Other vital substances (soy protein* * )
Legend:* Risk group* * Therapy
Note: The listed vital substances are not a substitute for drug therapy. Dietary supplements are intended to supplement the general diet in the particular life situation.