The purpose of this two-part study is to investigate the safety, tolerability and efficacy of LY3016859 after multiple intravenous (IV) dosing's in participants with diabetic nephropathy (DN). Part A will be dose escalation for safety and tolerability and Part B will evaluate Proteinuria.

Inclusion Criteria:

• Stable diabetic kidney disease (DKD) while taking Standard of Care medication (SOC), as defined by:

  • Estimated glomerular filtration rate (eGFR) less than (<) 90 milliliter per minute per 1.73 square meter (ml/min/1.73m²) as determine utilizing the Modification of Diet in Renal Disease (MDRD) equation
  • Taking an angiotensin convertible enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) at a stable dose for greater than or equal to (≥) 2 months prior to randomization and agree to continue to take such throughout the duration of the study
  • Type 1 or Type 2 diabetes on a stable treatment regimen and adequately controlled in the opinion of the investigator
  • First morning protein-creatine ratio (PCR) at screening ≥400 milligrams per gram (mg/g) (Part B only)

• Clinical chemistry labs within acceptable range for the participant population, as per investigator judgment

• Men and women of non-childbearing potential as determined by medical history and physical examination

  • Non-vasectomized male participants must agree to use a medically accepted method of contraception with all sexual partners during the study and for 90 days following the final dosing. Medically accepted effective forms of contraception may include condoms with contraceptive foam or having partners use diaphragms with contraceptive jelly or cervical caps with contraceptive jelly
  • Female participants must be postmenopausal or surgically sterile to participate in this study. This is defined as females between age 45 to 75 years, inclusive, and either 12 months without a menstrual period [no follicle stimulating hormone (FSH) test required] or 6-12 months without a menstrual period and follicle stimulating hormone (FSH) greater than (>) 40 international units per liter (IU/L)

• Must weigh ≥50 kilograms (kg) at time of screening and dosing

• Acceptable sitting blood pressure (BP) per the following American Heart Association (AHA) guidelines:

  • Normal: systolic blood pressure (SBP) <120 millimeters of mercury (mmHg) and diastolic blood pressure (DBP) <80 mmHg
  • Prehypertension: SBP 120-139 or DBP 80-89
  • High Blood Pressure (Hypertension) Stage 1: SBP 140-159 mmHg or DBP 90-99

• Have given written informed consent prior to any study-specific procedures

• Are reliable and willing to make themselves available for the duration of the study and are willing to follow site specific study procedures

• Have venous access sufficient to allow blood sampling

• Have laboratory values and other safety parameters that are, in the opinion of the investigator, acceptable fo participation for the study

Exclusion Criteria:

• Have a diagnosis of chronic kidney disease (CKD) other than DKD, (hypertensive nephrosclerosis superimposed on DKD is acceptable)

• Have SBP >160 mmHg or DBP >100 mmHg

  o Individuals with Stage 1 BP elevation (SBP 140-159 mmHg or DBP 90-99 mmHg) on some occasions during study, may be acceptable, as long as only non-protein-lowering antihypertensives are adjusted to achieve target BP goals (<140/90 mmHg)

• Current use of (or within 2 weeks of enrollment), or projected need for a renin inhibitor or aldosterone antagonist, or a combination of Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB)

• Individuals in whom dialysis or transplantation is anticipated within 6 months of screening

• Have a history of acute kidney injury within 3 months of screening

• Are currently enrolled in, or discontinued within the last 60 days from, a clinical trial involving an investigational drug that has not received regulatory approval for any indication and/or have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives of the administered drug (whichever is longer) prior to dosing

• Have previously completed or withdrawn from this study or any other study investigating LY3016859

• Have a diagnosis of Class III or IV congestive heart failure (as defined by the New York Heart Association)

• Have an abnormality in the 12-lead Electrocardiogram (ECG) that, in the opinion of the investigator increases the risks associated with participating in the study. In addition, individuals with the following findings will be excluded:

  • Confirmed corrected QT (QTcF) interval >450 milliseconds (msec) for men and >470 msec for women
  • Irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular ectopic beats
  • History of unexplained syncope
  • Family history of unexplained sudden death or sudden death due to long QT syndrome
  • T-wave configurations are not of sufficient quality for assessing QT interval, as determined by the investigator

• Have evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies; have a history of cirrhosis or hepatitis C or are positive for hepatitis C antibody at the screening visit; are known to be hepatitis B surface antigen-positive or are positive for hepatitis B surface antigen at the screening visit

• Are unwilling to discontinue use of Chinese herbs for at least 2 weeks prior to randomization and for the duration of their study participation

• Are unwilling or unable to comply with the use of a data collection device to directly record data from the participant

• Have donated blood of more than 500 milliliters (mL) within the last 60 days prior to screening

• Have an average weekly alcohol intake that exceeds 21 units per week or are unwilling to stop alcohol intake within 48 hours of entry into study and for the duration of the study (1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)

• Individuals who, in the opinion of the investigator, show evidence of regular use of drugs of abuse

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

All randomized participants who received at least one dose of study drug.